Abstract: Objective：To compare the efficacy between sunitinib and sorafenib in the first-line therapy on metastatic renal cell carcinoma (mRCC). Methods：Totally 261 mRCC patients from June 2009 to June 2017, including 112 treated with orally administrated sorafenib and 149 treated with orally administrated sunitinib, were retrospectively analyzed. The treatment schedule of sunitinib was 50 mg, qd, 4 weeks on and 2 weeks off for 1 cycle, while that of sorafenib was 400 mg, bid, 1 month for 1 cycle. Safety assessment was performed every 1 cycle. Imaging examinations were performed every 2 cycles to evaluate the efficacy. For patients with progressive disease, the dose escalations were performed when sorafenib was well tolerated. Results：The median progression free survival (PFS) of sorafenib and sunitinib were 15.5 and 20.0 months, respectively. The median overall survival (OS) of sorafenib and sunitinib were 31.5 and 36.0 months. All the patients were followed up for 3 to 96 months. The disease control rate of sorafenib group was 63.4%, being significantly lower than that of sunitinib group (83.2%, P<0.001). The adverse drug reactions were well controlled and tolerated in both groups. Conclusions：Sunitinib and sorafenib are both effective in treatment of mRCC, especially sunitinib with better disease control rate, and the adverse drug reactions can be well controlled.