A man crushed by agony cries out against the unfairness of his fate. He is suffering deeply, yet he knows with absolute certainty that he has done nothing to deserve it. His moral record is spotless, both in how he treats others and in how he approaches God.
The primary approach among commentators is that Job is expressing sheer confusion over his situation. He is enduring terrible pain for no reason, having never committed any act of cruelty or injustice [מצודת דוד, מלבי״ם, ביאור שטיינזלץ]. He insists that his suffering has come despite the complete absence of wrongdoing in his hands [רמב״ן]. However, an ironic view suggests that his troubles came upon him specifically because he avoided wrongdoing and maintained pure prayers, noting that wicked people often escape such severe hardships [רמב״ן].
Beyond his physical actions, Job defends the absolute purity of his prayers. This purity is understood in several ways. It can mean that his focus toward God was perfect, completely free from distracting or foreign thoughts [מצודת דוד]. Alternatively, the purity of his prayer reflects his relationship with other people; he never once used his prayers to curse another person or wish harm upon them [רש״י]. Taking a more legal view, the purity of his prayer means he is confident that his case is righteous and that he will ultimately win in judgment before God [מלבי״ם].
These two claims—having clean hands and offering pure prayer—are closely linked. A person whose hands are stained by theft or violence cannot expect God to listen to his prayers. Therefore, Job argues that because he is entirely innocent of robbery, his prayers are naturally pure and worthy of being accepted by God [חומת אנך]. Taking this connection even further, the very fact that Job was widely known as a man whose prayers were answered serves as the ultimate proof of his innocence. If his hands had been dirtied by violence, his prayers would have been ruined and ignored [אלשיך].