Abstract Background Previous experimental studies have shown an antagonistic interaction between cadmium and selenium. We explored the interaction between cadmium and selenium on human breast cancer risk. Methods A case–control study, enrolled 240 incident invasive breast cancer patients and 246 age-matched controls from 2 hospitals, was conducted in Guangzhou, China. Inductively coupled plasma mass spectrometry was used to examine urinary concentrations of cadmium and selenium. Association and interaction of the metal levels with breast cancer risk were tested using generalized additive and logistic regression models. Results As continuous variables, urinary cadmium [OR (95% CI): 1.16 (1.01–1.34)] but not selenium was significantly linearly associated with breast cancer risk. As tertiles, urinary cadmium did not significantly increase breast cancer risk; whereas women with the second tertile of selenium concentration had a significantly decreased risk of breast cancer as compared with those in the lowest tertile [OR (95% CI): 0.50 (0.30–0.81)]. Among the women with the lowest tertile of selenium, the highest tertile of cadmium significantly increased the risk of breast cancer [OR (95% CI): 2.83 (1.18–6.86)] compared to the lowest tertile of cadmium. A multiplicative interaction was found between tertiles of cadmium and selenium on breast cancer risk (P=0.018), particularly among postmenopausal women. Conclusions These results suggested that the association of urinary cadmium with breast cancer risk was modified by urinary selenium.