Objective: To evaluate the effect of Sunitinib therapy on immune function of patient with advanced renal cell carcinoma. Methods: A total of 27 patient with advanced renal cell carcinoma who received Sunitinib therapy in Chongqing Cancer Hospital from July 2010 to July 2014 were recruited in a prospective cohort study.Nineteen were male patients and 8 were female patients aged from 36 to 75 years with mean age of (58±7)years.Twenty-five cases were renal clear cell carcinoma, the other two cases were papillary renal cell carcinoma and Xp11.2 translocation renal cell carcinoma.According to MSKCC terminal prognosis scoring recommend by NCCN: 22 cases were in low risk, 5 cases were in high risk.All the patient took Sunitinib 50 mg orally once daily for 4 weeks, followed-up by 2 weeks.Flow cytometry was used to detect the levels of CD3+ , CD8+ , CD4+ T lymphocyte, NK cell and B lymphocyte in peripheral blood of patients before taking medicine.The levels of CD3+ , CD8+ , CD4+ T lymphocyte, NK cell, B lymphocyte in peripheral blood were detected again after 4 weeks, 6 weeks, 10 weeks and the disease progression.Paired t-test was used to analyze the data comparison of two groups, mean comparison in groups was conducted with repeated measurements analysis of variance, and the pairwise comparison was performed with LSD-t method. Results: The levels of CD3+ , CD8+ T lymphocyte, NK cell, B lymphocyte were significantly increased after the therapy of Sunitinib for 1 cycle(I-J was 212±22, 163±18, 59±12, 13.8±1.4, respectively, all P<0.05). The levels of CD3+ , CD8+ T lymphocyte, NK cell, B lymphocyte were significantly increased after the therapy of Sunitinib for 2 cycles(I-J was 362±43, 299±28, 91±19, 28.1±3.9, respectively, all P<0.05), while the level of CD4+ lymphocyte was decreased, but no significant difference(F=0.873, P>0.05). CD4+ /CD8+ was significantly decreased after the therapy of Sunitinib for 1 cycle, and it went on decreasing after the therapy of Sunitinib for 2 cycles(I-J was -0.31±0.03, -0.44±0.04, respectively, all P<0.05). Disease progression occurred in 10 cases during the follow-up period.The NK cell, CD3+ , CD4+ , CD8+ T lymphocyte were significantly decreased when the disease progressed(t=2.39-5.769, all P<0.05). Conclusions: Sunitinib has effect on the immune function of patients with advanced renal cell carcinoma, and the progression of renal cell carcinoma is related to the immune function.It suggests that targeted drug therapy should be combined with biological immunotherapy, which may be the research direction for the treatment of advanced renal cell carcinoma.