To investigate the effects of minimally invasive esophagectomy (MIE) and open esophagectomy (OE) on circulating tumor cell (CTC) level of elderly patients with esophageal cancer (EC). A total of 78 elderly EC patients who aged over 64 years were divided into the MIE group (n = 40) and the OE group (n = 38). CTC enrichment was performed through CD326 (EpCAM) immunomagnetic beads positive sorting, and then labeled by CK-PE and CD45. The quantity of CTCs was measured by multiparameter flow cytometry. Double antibody sandwich enzyme-linked immuno sorbent assay ELISA (DAS-ELISA) was used for detecting the levels of IL-6, IL-10, and IFN-gamma. Among the 78 elderly EC patients, CTC level after the surgery was higher than that during the surgery, and CTC level during surgery was higher than that before the surgery (both P < 0.05). Postoperative CTC level in the MIE group was lower than that in the OE group, and the variation of CTC level from pre-operation to intra-operation in the MIE group was also lower than that in the OE group (both P < 0.05). Furthermore, there was significant difference in the incidences of intra-operative and postoperative complications between the MIE group and the OE group (17 cases vs. 31 cases, P < 0.05), and the CTC levels of the patients with complications in either group were significantly higher than the patients without complications (both P < 0.05). IL-6 and IL-10 levels significantly increased, while IFN-gamma level decreased in both groups during the surgery and 3 days after the surgery compared to those before the surgery; 2 weeks after the surgery, IL-6 and IL-10 levels in the MIE group recovered to the pre-operative levels (all P < 0.05). However, in the OE group, IL-6 and IL-10 levels 2 weeks after the surgery were still significantly higher than those before the surgery (all P < 0.05); IFN-gamma levels in both groups recovered to the pre-operative levels, with higher level in the MIE group than that in the OE group (P < 0.05). MIE helped to reduce the survival rate of tumor cells in peripheral blood at the early period of postoperation, and dynamic monitoring CTC level could be used to evaluate the prognosis of EC patients.