We performed a phase II trial of docetaxel in combination with capecitabine to evaluate the antitumor response, toxicity, and survival in pre-treated patients with advanced esophageal squamous cell carcinoma. Patients with advanced esophageal squamous cell carcinoma who had failed first-line chemotherapy with cisplatin and 5-fluorouracil were enrolled in this study. Treatment consisted of oral capecitabine (825 mg/m(2) twice daily on days 1-14) plus 1-h intravenous docetaxel (60 mg/m(2) on day 1) every 3 weeks for up to 6 cycles. Between June 2008 and August 2011, thirty eligible patients with a median age of 58 years (range 38-68 years) were enrolled. Patients received a median of three cycles of treatment (range 1-6). The median follow-up was 15.4 months (range 1.0-31.5 months). Intent-to-treat efficacy analysis demonstrated an overall response rate of 23.3% (0 complete response and 7 partial response) and stable disease of 43.4 % (n = 13). The median time to progression was 3.0 months (95% CI 1.9-4.1 months). The median survival was 8.3 months (95% CI 6.8-9.8 months). Severe adverse events (grade 3/4) reported were as follows: neutropenia (33.3%, n = 10, including febrile neutropenia 6.7%, n = 2), anemia (16.7%, n = 5), thrombocytopenia (10 %, n = 3), hand-foot syndrome (13.3%, n = 4), and fatigue (10%, n = 3). Docetaxel plus capecitabine had a manageable adverse event profile and promising activity in advance esophageal squamous cell carcinoma as a second-line treatment.