Objective To investigate the effect of neoadjuvant chemotherapy combined with surgery on circulating tumor cells and survival rate of local advanced esophageal cancer.Methods Between June 2010 and June 2015, 110 patients with locally advanced esophageal cancer treated in our hospital were randomized into the observation group and control group. Patients in the observation group were treated with neoadjuvant chemotherapy before operation, while those in the control group were treated surgically alone. The postoperative survival rate of the two groups was compared. At the same time, immunoenrichment and immunofluorescence staining were used to identify and isolate the circulating tumor cells (CTCs) in the peripheral blood. The levels of CTCs in peripheral blood were detected before and after treatment. All patients were followed up for 3 years and the short-term survival rates of the two groups were recorded.Results There was no significant difference in the levels of CTCs between the two groups before treatment. In the first, second, and third years after treatment, the CTC values in the peripheral blood of the observation group were 6.88, 6.56 and 7.20, respectively, compared with 12.8, 13.0 and 13.2 respectively in the control group. The levels of CTCs of the observation group were significantly lower than those of the control group (P<0.05). The 1 -, 2 -, and 3 - year survival rates in the observation group were 96.36%, 89.09% and 65.45%, respectively, compared with 78.18%, 56.36% and 34.55% respectively in the control group.Conclusions Neoadjuvant chemotherapy combined with surgery can reduce the malignancy of local advanced esophageal cancer, and improve the short-term efficacy as well as the survival rate of patients.