Introduction: Discrimination is a commonly perceived stressor among African Americans and Latinos, and previous research has linked stress with substance dependence. Although studies have shown a link between discrimination and smoking, little is known about the relationship between discrimination and nicotine dependence. Methods: A total of 2,376 African American (33.4%; n = 794), Latino (33.1%; n = 786), and White (33.5%; n = 796) smokers completed an online survey. Everyday discrimination experiences were described in total and by race/ethnicity. Covariate-adjusted linear regression analyses were conducted to evaluate the associations between everyday discrimination and indicators of nicotine dependence. Results: Most participants (79.1%), regardless of race/ethnicity, reported experiencing everyday discrimination. However, total scores on the discrimination measure were higher among Latinos and African Americans than among Whites (p < .001). Race/ethnicity/national origin was the most commonly perceived reason for everyday discrimination among African Americans and Latinos, whereas physical appearance was the most commonly perceived reason among Whites. Regression analyses indicated that everyday discrimination was positively associated with indicators of nicotine dependence, including the Heaviness of Smoking Index (HSI; p < .001) and the Brief Wisconsin Inventory of Smoking Dependence Motives (WISDM) scales (all ps < .001). There was a significant interaction between race/ethnicity and discrimination, such that discrimination was associated with the HSI only among Latinos. Similarly, discrimination was most strongly associated with the WISDM scales among Latinos. Conclusions: Analyses indicated that discrimination is a common stressor associated with nicotine dependence. Findings suggest that greater nicotine dependence is a potential pathway through which discrimination may influence health.