The prognostic value of Ki-67 expression in small cell carcinoma of the esophagus (SCCE) has not been explored in any previous studies. Therefore, we conducted this retrospective study to investigate the prognostic role of Ki-67 in SCCE for the first time. A total of 44 patients were included for analysis. The baseline clinicopathological data of these SCCE patients shared similar characteristics with previous studies. Ten patients were at stage I, 17 at stage II, and the remaining 17 were at stage III. Postoperatively, 23 patients received adjuvant therapy. Twenty-eight patients were found to have a high expression of Ki-67 (> 50%). After a median follow-up time of 54.8 months, the median survival time of those patients was 22.1 months. Early TNM stage, application of adjuvant therapy, and high expression of Ki-67 (Hazard Ratio = 0.314, 95% CI: 0.127-0.774; P = 0.012) were found to be favorable prognostic factors of patients with SCCE. In subgroup analysis, adjuvant therapy could only bring significant survival benefit for patients with high expression of Ki-67 (P = 0.008). Patients undergoing esophagectomy with lymphadenectomy for SCCE from January 2009 to January 2015 in our department were retrospectively analyzed. Data for analysis included demographic data, pathologic findings, tumor stage, adjuvant therapy, and survival time as well as Ki-67 index. This study suggested that high expression of Ki-67 may not only serve as a favorable prognostic factor of SCCE but also an indication of providing adjuvant therapy for SCCE patients with surgical resection.