Abstract: Objective: This study aims to utilize data from the National Health and Nutrition Examination Survey (NHANES), which was conducted in the United States from 2009 to 2014, to investigate the risk of chronic drug-induced liver injury (DILI) in patients with psoriasis and to establish a risk prediction model via machine learning. Methods: A total of 6,303 participants were selected, all of whom answered questions regarding psoriasis and drug use. Chronic DILI was diagnosed on the basis of persistent abnormalities in the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL) levels. Multiple logistic regression and other methods have been employed in different models to explore the relationship between psoriasis and chronic DILI. Potential confounding factors (age, sex, ethnicity, household income, education, alcohol consumption, smoking, and body mass index (BMI)) were controlled. Results: After controlling for potential confounding factors, the results revealed a significant positive correlation between psoriasis and chronic DILI, and an optimal predictive model was generated on the basis of diabetes status and BMI. Conclusion: Patients with psoriasis appear to be at increased risk of chronic DILI. More prospective studies are needed to confirm this clinical correlation.