OBJECTIVE To system atically evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs）versus routine second-line chemotherapy in the treatment of advanced esophageal cancer ，and to provide evidence-based reference for clinical medication. METHODS Randomized controlled trials （RCTs） about ICIs （trial group ） versus routine second-line chemotherapy （control group ） in the treatment of advanced esophageal cancer were searched from PubMed ，Embase，The Cochrane Library ，CNKI，Wanfang and VIP databases from the inception to August 1st，2021. After screening the literature and extracting data ，the risk of bias assessment tool recommended by Cochrane Systematic Evaluator Manual 5.1.0 was used to evaluate the quality of the included literature ，and RevMan 5.4.1 software was used for meta-analysis and sensitivity analysis. RESULTS A total of four studies were included ，involving 1 656 patients. Meta-analysis results showed that the overall survival of trial group was significantly longer than control group [HR ＝0.79，95％CI（0.71，0.88），P＜0.000 1]；the incidence of grade 3 or higher adverse events in trial group was significantly lower than control group [RR ＝0.42，95％CI（0.32，0.54），P＜0.000 01]. But there was no significant difference in progression-free survival [HR ＝0.95，95％ CI （0.75，1.21），P＝0.70] or objective remission rate [RR ＝1.72，95％CI（0.95，3.13），P＝0.07] between 2 groups. Results of subgroup analysis was performed according to the expression of programmed death ligand 1 showed that overall survival of patients with tumor proportion score （TPS）≥1％ in trial group was significantly longer than control group [HR ＝0.64，95％CI（0.51，0.79），P＜0.000 1]；there was no significant difference in overall survival of patients with TPS ＜1％ between 2 groups [HR ＝0.83，95％CI（0.67，1.02），P＝0.07]. The results of sensitivity analysis showed that except for the objective remission rate ，the conclusions of other indicators were robust. CONCLUSIONS Compared with routine second-line treatment ，ICIs can prolong overall survival and has good safety ，but shows no advantage in ） terms of progression-free survival and objective response rates.