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People with HIV smoke cigarettes at a high prevalence, and it is important to identify modifiable variables related to smoking in this population. Race/ethnicity-based discrimination is common among people with HIV from minoritized racial and ethnic groups and results in significant adverse effects. The goal of this study was to examine the relationship between race/ethnicity-based discrimination, depression, and smoking-related variables among people with HIV who smoke. This was a secondary analysis of data from a prospective, randomized controlled smoking cessation trial for people with HIV. Participants were recruited from three HIV clinical care sites and randomly assigned to an HIV-tailored group therapy intervention or a control condition. Participants completed measures of demographics, smoking-related variables, race/ethnicity-based discrimination, and depressive symptoms at baseline and were followed up 3- and 6-months after study completion. Depressive symptoms had an indirect effect on the relationship between race/ethnicity-based discrimination and self-efficacy to quit smoking at 3-month follow-up. Depressive symptoms mediated the relationship between race/ethnicity-based discrimination and both nicotine dependence and self-efficacy to quit smoking at 6-month follow-up. Findings highlight the importance of considering race/ethnicity-based discrimination and depressive symptoms in the development and implementation of smoking cessation treatment interventions for people with HIV. [ABSTRACT FROM AUTHOR]