Abstract Background Clarification of the factors associated with decreased physical activity is crucial for effective disease management in patients undergoing hemodialysis. Although evidence suggests that physical activity may be associated with physical function or depressive symptoms, limited studies have demonstrated these factors to be independently associated with the former in patients undergoing hemodialysis. This study aimed to examine whether physical function and depressive symptoms were independently or interactively associated with daily physical activity in patients undergoing hemodialysis. Methods This cross-sectional study analyzed 157 clinically stable outpatients (median age: 68 years) receiving hemodialysis. Physical activity (steps/day) was measured using an accelerometer for four consecutive non-dialysis days. Physical function was evaluated by calculating usual walking speed along a 10-m walkway. The 10-item version of the Center for Epidemiologic Studies for Depression Scale was used to assess depressive symptoms. Results The hierarchical multiple regression model (Model 2), constructed by adding physical function to Model 1 (clinical characteristics), showed a significant increase in coefficient of determination (R 2), compared to Model 1 (ΔR 2 = 0.15, P