Objective To investigate the toxicities of sorafenib in the treatment of advanced re-nal cell carcinoma, and discuss the management. Methods Fifty-eight patients with advanced renal cell carcinoma were treated with sorafenib from March 2006 to February 2008. Of them, 44 were males and 14 were females with the average age of 50 years. Single agent of sorafenib 400 mg twice daily was administrated to 49 patients, and the other 9 patients were given sorafenib and Interferon-a as a combination therapy. The main toxicities such as hand-foot syndrome, alopecia, rash, mucositis, fatigue, diarrhea, weight loss, hypertension, hemoptysis, liver dysfunction, hypophosphatemia and anemia were analyzed for their occurrence time, duration, and grade. Results The toxicities of sor-afenib included hand-foot skin reaction (75.9%), alopecia (67.2%), rash (39.7%), mucositis (24.1%), fatigue (74.1%), hypertension (24.1%), and liver dysfunction (13.8%). Twelve cases (20.7%) experienced grade 3 toxicities and had dose reduced; and two cases encountered grade 4 tox-icities and had permanent withdraw. Conclusions There is peculiarity in treating Chinese advanced renal cell carcinoma patients with sorafenib. The incidences of major toxicities of sorafenib are higher in Chinese patients than what have been observed in studies conducted in US and Europe. Toxicities such as hemorrhage and angina could also appear and need carefully monitored. Generally, most of the toxicities of sorafenib are grade 1 and 2, and easy to be managed in clinic.