OBJECTIVE To evaluate the cost-effectiveness of tislelizumab monotherapy in the second-line treatment of advanced or metastatic esophageal squamous cell carcinoma （ESCC），so as to provide reference for rational use of drug in clinic. METHODS A three-state partitioned survival model was constructed from the perspective of China’s health system， based on the data of RATIONALE-302 study，with simulation time limit of 10 years， cycle period of 1 month. The incremental cost-effectiveness ratio （ICER） was calculated with quality-adjusted life year （QALY） as utility index. The cost-effectiveness of tislelizumab monotherapy was compared with that of chemotherapy for second-line treatment of advanced or metastatic ESCC by cost-utility analysis. The stability of basic analysis results was validated through sensitivity analysis and scenario analysis. RESULTS The results of basic analysis showed that compared with chemotherapy group， incremental cost per capita of tislelizumab group was 35 025.32 yuan，and incremental utility per capita was 2.71 QALYs； ICER was 12 892.31 yuan/QALY， which was far lower than the willingness-to-pay （WTP） threshold of 3 times of China’s per capita gross domestic product （GDP） 242 928 yuan in 2021. The results of univariate sensitivity analysis showed that parameters such as the cost of apatinib， the utility value of disease progression status and the cost of adverse reactions in the chemotherapy group had a great impact on the ICER value， but these parameters could not cause the reversal of the basic analysis results. Probabilistic sensitivity analysis showed that WTP threshold was higher than 80 000 yuan/QALY，the probability of tislelizumab monotherapy possessed cost-effectiveness was 100%. Results of scenario analysis showed that in which model simulation time lasted for 5 or 20 years，ICER of tislelizumab was 8 331.00 yuan/QALY and 12 981.00 yuan/QALY， which were less than 3 times of China’s per capita GDP in 2021 as WTP threshold. CONCLUSIONS When three times of China’s GDP per capita in 2021 is taken as the WTP threshold， the second-line treatment of tirelizumab monotherapy for advanced or metastatic ESCC is more cost-effective than chemotherapy.