Objective: The optimal neoadjuvant chemoradiotherapy (CRT) regimen in esophageal cancer has not yet been defined. This study was aimed to compare the differences in pathologic response and survival between docetaxel/cisplatin and fluorouracil/cisplatin as neoadjuvant CRT in locally advanced esophageal squamous cell carcinoma (SCC). Methods: We retrospectively analyzed patients with thoracic esophageal SCC who received neoadjuvant CRT followed by esophagectomy from 2000 to 2014. After adjusting for sex, age, performance status, tumor length, tumor location and clinical TNM stage, 32 docetaxel/cisplatin-treated patients were matched to 62 patients who received fluorouracil/cisplatin at a ratio of 1:2. Treatment toxicity, pathologic complete response (pCR) and survival outcomes were compared between groups. Results: Baseline characteristics were well balanced between groups. The pCR rate in the docetaxel/cisplatin group was higher than that in the fluorouracil/cisplatin group but without significant difference (40.6% vs. 30.6%, P = 0.333). The 3-year overall survival rate in the docetaxel/cisplatin group was 64.9% versus 46.0% in the fluorouracil/cisplatin group (P = 0.039). There were no significant differences in incidence of treatment toxicity during CRT or surgical complications between groups, with the exception of Grade 3-4 hematologic toxicity (37.5% vs. 17.7%, P = 0.035), which was more frequent in the docetaxel/cisplatin group. Conclusions: Docetaxel/cisplatin might be associated with more favorable survival than fluorouracil/cisplatin in esophageal SCC treated with neoadjuvant CRT. Prospective validation is warranted.