Background: Neoadjuvant chemotherapy with or without radiotherapy are the common treatments for locally advanced squamous-cell esophageal cancer(ESCC). There is no sufficient data to choose between these two effective therapies. The aim of our retrospective study was to compare the clinical efficacy between these two strategies of complete pathological response (pCR), postoperative morbidity, mortality, and overall and disease-free survival in patients with locally advanced ESCC. Methods: Patients with stage T2-4N0-1M0 squamous-cell esophageal cancer at our institution were recruited, including patients who underwent NCRT (1 cycle of cisplatin and 5-fluorouracil with concurrent radiotherapy) or NCT (2 cycles of cisplatin and 5-fluorouracil only ) before esophagectomy. Results: From January 2009 to October 2015, a total of 177 patients were analyzed, with 72 received NCRT and the remaining 105 received NCT. The pathological complete response (pCR) rate was 22.2% (n = 16) in NCRT group and 9.5% (n = 10) in NCT group (P= 0.019). The postoperative mortality was 1.4% in NCRT group, versus 4.8% in NCT group. The postoperative morbidity was 20.8% in NCRT group, versus 27.6% in NCT group. There was no significant difference in recurrence between the two groups (P= 0.397). 1-,2-,3-year overall survival rates in NCRT and NCT group were 87%, 74%, 51% and 81%, 64%, 51%, respectively (P= 0.527), and 1-,2-,3-year DFS rates were 77%, 54%, 50% and 65%, 54%, 46%, respectively(P= 0.379). Conclusions: For patients with locally advanced squamous-cell esophageal cancer, the addition of radiotherapy to neoadjuvant chemotherapy may result in higher complete pathological response with acceptable postoperative mortality and morbidity, while the long-term survival benefit is not significant.