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An inflammatory skin condition called psoriasis results from immune system interactions that are out of balance. Reactive oxygen species are produced as a general mechanism of mercury toxicity. This study aimed to determine whether there was an association between blood total mercury and psoriasis in US adults. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2005–2006 and 2013–2014. NHANES is a national research survey program every two years to assess the population’s nutritional and physical health. The relationship between blood total mercury and psoriasis was studied using multivariable logistic regression models and smooth curve fitting. Subgroup analysis and interaction tests were used to investigate if this association was stable across populations. After adjusting for several factors, we found a positive association between blood total mercury and psoriasis in 6086 participants. According to the fully adjusted model, each 1-unit increase in blood total mercury was associated with an 8% increase in the prevalence of psoriasis [1.08 (1.03, 1.14)]. The favorable association seems to be more pronounced in non-diabetes. Our research shows a positive association between psoriasis and blood total mercury in US adults. The results of this study need to be supported by additional prospective research.