Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a primary pungent and irritating ingredient in chilies and “hot” red peppers, which are widely used as spices. It is a specific neurotoxin for type C unmyelinated vesical afferent fibers and reorganization of voiding reflexes in disease. Topical capsaicin is know to be a safe and effective pain management adjunct for rheumatoid arthritis, osteoarthritis, neuralgias, diabetic neuropathy, and the treatment of pain derived from oral disease. Numerous studies indicated that capsaicin has the antimutagenic and anti-carcinogenic activity. Interleukin-6 (IL-6) is produced at high levels by renal cell carcinoma (RCC) and plays an important role. The effect of capsaicin on RCC (786-O and A498) is still unclear. This study is to investigate the effect of capsaicin on IL-6 secretion from RCC. A498 and 786-O cells were cultured in RPMI-1640 with different concentrations of capsaicin with/without PMA. The media IL-6 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). The cell cycle of RCC was measured by flow cytometry. The results showed that: (1) significant increase of IL-6 from 786-O and A498 treated with capsaicin only for 24 hours; (2) capsaicin with PMA stimulate the IL-6 secretion from A498 and 786-O cells; (3) cell cycle arrest at G0/G1 phase were observed for A498 and 786-O treated 200 μM capsaicin for 24 hr. Taken together, these data demonstrated that the stimulatory effect of capsaicin on IL-6 secretion from RCC is, at least in part, through the regulation of cell cycle on RCC cell lines.