Conflicting results regarding the impact of selenium on reducing prostate cancer have been reported. The current analysis aimed to understand whether there are potential factors affecting the relationship between selenium and prostate cancer.To clarify the relationship between dietary selenium intake and prostate cancer, we evaluated the correlation between dietary selenium intake and prostate-specific antigen (PSA) based on the National Health and Nutrition Examination Survey (NHANES) database.After screening the NHANES survey data from 2005 to 2010, data for 3,614 of 31,034 participants were considered suitable to include in our study. Dietary selenium intake was the independent variable of our study, while PSA was the dependent variable. We stratified participants into current, former, and never smokers and performed an interaction test on the relationship between selenium intake and PSA using multivariable logistic regression for each smoking-status subgroup.For our subgroup analysis, we grouped participants based on smoking status and investigated the association between dietary selenium intake and PSA levels. Among the 242 participants with a PSA level of 4 or higher, the mean age was 58.5 years (±12.1). After adjusting for covariates, we did not find a significant association between dietary selenium and the odds of having a high PSA level. However, we observed a significant interaction between smoking status and dietary selenium in relation to PSA levels (P = .007). Specifically, smokers had lower odds of having high PSA levels, while nonsmokers had higher odds. This suggests that smoking status may modify the effect of dietary selenium on PSA levels.Our findings suggest that smoking status affects the relationship between dietary selenium intake and PSA and that smokers are at lower odds of having a high PSA level.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.