Wan-Xiang Zheng,* Fei Yan,* Qin Xue, Guo-Jun Wu, Wei-Jun Qin, Fu-Li Wang, Jun Qin, Chun-Juan Tian, Jian-Lin Yuan Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Background: We analyzed the expression of heme oxygenase-1 (HO-1) in patients undergoing radical nephrectomy for advanced clear cell renal cell carcinoma (CC-RCC) and evaluated the effects of the targeted therapies treated with sorafenib and sunitinib. Methods: Expression of HO-1 in cancer tissue from 66 patients was measured by immunohistochemical staining. The patients received either oral sorafenib (n=40) or oral sunitinib (n=26) within 4 weeks after nephrectomy and were followed up long term to determine the tumor response and prognosis. Results: Our current study revealed a high HO-1 expression level in 57.6% (38/66) of patients and a low HO-1 expression level in 42.4% (28/66) of patients with CC-RCC. The study also revealed that patients with high HO-1 expression did not have a higher objective response rate (2.6% versus 53.6%, P