The incidence of renal cell carcinoma (RCC) has been steadily rising each year. There are currently few recognized biomarkers for the diagnosis and prognosis of RCC. We investigated semenogelin I (Sg I) expression and its clinical significance in patients with RCC. The expression levels of Sg I and its protein were measured by qPCR and Western blotting, respectively. Immunohistochemistry was used to investigate the protein expression of Sg I in RCC and normal renal tissue from 53 patients. The Kaplan-Meier method and log-rank test were used to evaluate the data. By qRCR (p < 0.01) and Western blot, the level of Sg I expression in benign tissues was higher than that in RCC tissues. Expression of Sg I was observed in 30 (57 %) RCC cases, which was significantly lower than that observed in benign renal tissues from the same patients [Sg I positive in 53 (100 %) cases (p < 0.0001)] by immunohistochemistry. There was an inverse relation between Sg I expression and clinical stage (pT1-2 vs pT3-4, p < 0.0001). Patients with Sg I-negative tumor had a significantly higher risk of recurrence (Kaplan-Meier and log-rank tests, p < 0.0001). There was low Sg I expression in RCC. Sg I expression has potential value in predicting cancer progression and prognosis. These findings support the use of Sg I as a novel biomarker for RCC.