If he will contend with him - That is, if God enters into a controversy with man. If he chooses to charge crime on him, and to hold him responsible for his deeds. The language here is taken from courts of justice, and means that if a trial were instituted, where God should submit charges, and the matter were left to adjudication, man could not answer the charges against him; compare the notes at Isaiah 41:1.
He cannot answer him one of a thousand - For one of a thousand of the sins charged on him. The word "thousand" here is used to denote the largest number, or all. A man who could not answer for one charge brought against him out of a thousand, must be held to be guilty; and the expression here is equivalent to saying that he could not answer him at all. It may also be implied that God has many charges against man. His sins are to be reckoned by thousands. They are numerous as his years, his months, his weeks, his days, his hours, his moments; numerous as his privileges, his deeds, and his thoughts. For not one of those sins can he answer. He can give no satisfactory account before an impartial tribunal for any of them. If so, how deeply guilty is man before God! How glorious that plan of justification by which he can be freed from this long list of offences, and treated as though he had not sinned.

If he will contend with him - God is so holy, and his law so strict, that if he will enter into judgment with his creatures, the most upright of them cannot be justified in his sight.
One of a thousand - Of a thousand offenses of which he may be accused he cannot vindicate himself even in one. How little that any man does, even in the way of righteousness, truth, and mercy, can stand the penetrating eye of a just and holy God, when all motives, feelings, and objects, come to be scrutinized in his sight, on this ground, no man living can be justified. O, how necessary to fallen, weak, miserable, imperfect and sinful man, is the doctrine of justification by faith, and sanctification through the Divine Spirit, by the sacrificial death and mediation of the Lord Jesus Christ!

If he will contend with him, he cannot answer him one of a (b) thousand.
(b) Of a thousand things, which God could lay to his charge, man cannot answer him one.

If he will contend with him,.... If God will contend with man, so Sephorno; enter into a controversy with him, litigate and dispute the point in law, whether he is just or not, man cannot answer to the allegations he will produce; or if man should contend with God, a potsherd strive with its maker, to what purpose would it be? he could never avail himself by such a procedure; the match is unequal, there is no striving or contending with God in a judicial, way:
he cannot answer him one of a thousand; which some understand, that God will not answer men; he will not vouchsafe to give an answer to such that plead with him, or talk with him of his judgments in providence, or pretend to vindicate themselves, their ways, and their works, before him; but this sense seems contrary to Jeremiah 12:1; but the meaning is, that man cannot answer God; either not one man out of a thousand, that is, none at all; unless, by one of a thousand, is meant the interpreter, one among a thousand, even the Messiah, the chiefest among ten thousand; the one man of a thousand Solomon found upon search; see Job 33:23; he indeed has made himself responsible for his people, as their surety, and was able to answer for them; and he has answered for them, and made satisfaction for their sins; it was exacted, or required, that is, a full payment of their debts, or a plenary satisfaction for their sins, "and he answered", according to Isaiah 53:7; but rather the sense is, that a man cannot answer, either one time of a thousand (u), or one argument to one article exhibited, or to one objection or charge of a thousand brought against him by the law or justice of God; that is, for one sin of a thousand he has committed; so Mr. Broughton renders it, "to one thing of a thousand" (w); this suggests that the sins of men are numerous; their debts are many, they are more than ten thousand talents, which they are not able to answer to, or pay off, no, not one of them; their iniquities are more than the hairs of their head, they cannot be understood or reckoned: and now a man cannot answer for one of a thousand, or the millions of sins he is guilty of; he cannot deny them, he cannot excuse them, he cannot make satisfaction for anyone of them; they are committed against an infinite Being, and require an infinite satisfaction, which man cannot give; they are violations of a law, and injuries to divine justice, that no man is able to atone for; whatever obedience he is capable of, or does perform, God has a prior right unto it, and therefore can never answer for former transgressions; this being the case, sinful man cannot be just with God upon the foot of his works, which is the thing this observation is made to illustrate: man's obedience is so short, and God's commandment or law so very broad, that these two can never be brought to meet, agree together, or answer to one another; and therefore it may be strongly concluded that a man is justified, if ever he is justified at all, in the sight of God, by faith in Christ and his righteousness, without the deeds of the law, Romans 3:28.
(u) "una vice ex millibus", Schmidt. (w) "Ad rem unam ex mille", Beza; "ad unum argumentum ex mille argumentis", Vatablus; so Castalio, Bar Tzemach.

If he--God
will contend with him--literally, "deign to enter into judgment."
he cannot answer, &c.--He (man) would not dare, even if he had a thousand answers in readiness to one question of God's, to utter one of them, from awe of His Majesty.

One - One accusation among a thousand which God shall produce against him.