Background <p>Paranitrophenol, a metabolite of organophosphate insecticides, was associated with various adverse health outcomes. However, the association of Paranitrophenol with all-cause and cancer mortality in adults remains unclear.</p> Methods <p>A total of 3,362 participants (1680 male) were included from the National Health and Nutrition Examination Surveys (NHANES). Urinary Paranitrophenol was measured using ultra-high-performance LC-MS/MS. Mortality status and causes were obtained from National Death Index. Cox proportional hazards regression analysis was performed to explore the associations between Paranitrophenol and all-cause and cancer mortality, respectively.</p> Results <p>After a follow-up of 22.75 thousand person-years, there were 297 deaths from all causes and 69 deaths from cancer. Comparing with the lowest quartile, the highest quartile was not associated with all-cause mortality in the neither univariate model nor adjusted model. In terms of cancer mortality, the hazard ratios and 95% confidence interval of the highest quartile is 0.44 (0.21–0.93) in the univariate model, 0.40 (0.18–0.86) in the partly-adjusted model, and 0.40 (0.18–0.88) in the fully-adjusted model.</p> Conclusion <p>Higher urinary Paranitrophenol levels were associated with a decreased risk of cancer mortality. This association remained independent of demographics, lifestyle factors, and comorbidities.</p>