OBJECTIVES: To explore associations between fatalistic beliefs about cancer and self-reported use of dietary supplements (DS). METHODS: A cross-sectional study among American adults was conducted using Health Information National Trends Survey-Food and Drug Administration 2015 data. Primary outcome was DS usage (yes/no) in the past 12 months. Five fatalistic belief (agreement or disagreement) statements including DS prevent cancer, DS treat cancer, behavior/lifestyle causes cancer, everything causes cancer, and cancer prevention not possible were used to explore associations with DS usage. Weighted bivariate descriptive analysis to compare sociodemographics between users/non-users of DS, and adjusted multivariate logistic regression analysis were conducted to examine the associations. RESULTS: CONCLUSIONS: The use of DS is predominantly affected by the perceived belief that cancer can be avoided or treated through DS. These positive findings highlight the need for research in exploring the roles of DS in cancer prevention and treatment.