Background and Objectives We retrospectively studied the predisposing factors for nephrotoxicity in the patients with advanced esophageal squamous-cell carcinoma who received combination chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF therapy). Methods Between January 2010 and March 2014, 41 patients with Stage IB to III esophageal squamous-cell carcinoma received the DCF therapy (docetaxel 70-75 mg/m2, day 1; cisplatin 70-75 mg/m2, day 1; 5-fluorouracil 750 mg/m2, days 1-5) in our hospital. Renal dysfunction was defined as a creatinine clearance (Ccr) of less than 60 mL/min. Predictors of nephrotoxicity were identified through logistic-regression analysis. Results Nephrotoxicity developed in 20 patients and did not develop in 21 patients. Nephrotoxicity developed during the first course of DCF therapy in 16 patients, the second course in 3 patients, and the third course in 1 patient. The dose of DCF therapy was decreased in 8 patients with nephrotoxicity and 7 patients without nephrotoxicity. Multivariate analysis showed that a low Ccr level immediately before DCF therapy was an independent risk factor for the development of nephrotoxicity (odds ratio, 0.932; 95% confidence interval, 0.876 to 0.992; P = 0.027). On receiver operating characteristic curve analysis, the optimal cutoff value of Ccr for the development of nephrotoxicity was 75.8 mL/min. The 2-year overall survival rate was 84.2% in patients with nephrotoxicity and 90.0% in patients without nephrotoxicity (P = 0.635). Conclusions Low Ccr levels immediately before DCF therapy are a risk factor for the development of nephrotoxicity. Patients should therefore be carefully monitored.