The novel's title encapsulates a central irony of the novel: it reflects Nathan Price's mispronunciation of the native words for "Jesus is precious," such that the Congolese hear instead that "Jesus is poisonwood." Ironically, the Jesus preached to the Congolese by arrogant Western missionaries like Nathan is poison to the Congolese people, something they need to stay away from. People like Price, intending to bring salvation to the Congo, bring disaster.
Nathan represents the way white patriarchy comes into a native culture without any attempt to respect or understand the people with whom it is interacting. Nathan believes he comes from a far superior culture and has all the answers and nothing to learn. He tries to dynamite fish out of the water, in part to impress the Congolese, who are not impressed. He pays no attention to how the Congolese plant or farm. Ironically, if he had paid more attention to his hosts' way life and treated them as equal human beings, he would have had a greater chance of succeeding as a missionary—and of successfully surviving himself.
Another irony of the novel is that the supposedly inferior black villagers, though often damaged and crippled, are more competent and humane—more Christlike—than the Christians.