Background: Prognostic factors for overall survival (OS) of the patients with clear cell renal cell carcinoma (cRCC) treated with nephrectomy are still not defined well. Butyrylcholinesterase (BChE) is an α-glycoprotein found in the nervous system and liver. Advanced cancer is a condition with mild to moderate inflammation and interacts with various degree of protein-energy malnutrition. In this study, we analyzed the potential preoperative prognostic significance of BChE in patients with cRCC undergoing nephrectomy. Methods: etween 1992 and 2013, we treated 551 patients with renal cell carcinoma. Of these 400 patients with cRCC who underwent radical or partial nephrectomy were enrolled. Serum BChE was routinely measured before operation in all patients. Covariates included age, gender, performance status (PS), preoperative laboratory data, clinical T stage, and distant metastasis status. Univariate analyses were performed using the Kaplan-Meier and log-rank methods. Multivariate analysis was performed using a Cox proportional hazard model. Univariate and multivariate analyses were performed to determine clinical factors that associated with OS. Results: Of these, 302 patients had an organ-confined disease (T1-2N0M0) and 56 patients had a distant metastasis (any T, any N, and M1). The median BChE level was 250U/L (normal range from 168 to 470U/L). The median follow-up period was 34 months. At the time of analysis, 26 patients (6.5%) had alive with recurrent cRCC and 38 patients (9.5%) had died from cRCC. The 3-year OS rate for our entire cohort of 400 patients was 88%. The 3-year OS rates were 89.3% and 77.7% in the BChE ≥100 and <100U/L groups (p= 0.004). In the univariate analysis, PS, anemia, hypoalbuminemia, BChE, corrected calcium, C-reactive protein, and distant metastasis status were significantly associated with OS. Multivariate analysis revealed that BChE and distant metastasis status were significantly associated with OS. Conclusions: These data suggest a possible role of pre-operative BChE as an independent predictor of OS after nephrectomy for cRCC.