OBJECTIVE To evaluate the cost-effectiveness of nivolumab combined with ipilimumab in the first-line treatment of unresectable malignant pleural mesothelioma （MPM）. METHODS From the perspective of healthcare system ，a partitioned survival model were developed ，the cost-effectiveness of nivolumab combined with ipilimumab （dual-immunotherapy plan ）versus chemotherapy in the first-line treatment of unresectable MPM by cost-utility analysis. Clinical trial data were collected from CheckMate 743 study. Direct medical cost included drug costs ，disease management cost and cost of treatment of adverse reactions. Costs and utilities were discounted at an annual rate of 5％. The willingness to pay threshold was 3 times of gross domestic product （GDP）per capita in 2021 [242 928 yuan/QALY（quality-adjusted life year ）]. Scenario analysis was used to analyze and compare the two regimens under the scenario of complimentary drug for patients in dual-immunotherapy group. The robustness of the findings was evaluated by one-way sensitivity analysis and probabilistic sensitivity analysis. RESULTS Baseline analysis results showed that total cost of dual-immunotherapy regimen was higher than that of chemotherapy regimen ，and the utility was also better than that of chemotherapy plan ；the incremental cost-effectiveness ratio （ICER）was 417 122.2 yuan/QALY，which was higher than the willingness to pay threshold ；the dual-immunotherapy regimen was not cost-effective compared to the chemotherapy regimen. Under the scenario of complimentary drug ，the cost of dual-immunotherapy was 327 454.5 yuan，ICER was 75 664.1 yuan/QALY，which was lower than the willingness to pay threshold and resulted in a reversal of the baseline analysis. One-way sensitivity analysis showed that under the health states of progression free survival and progressive disease ，utility value and the price of nivolumab had a greater impact on the ICER value. Probabilistic sensitivity analysis showed that the results of baseline analysis were robust. CONCLUSIONS At a 163.com willingness to pay threshold of 3 times of GDP per capita in nivolumab combined with ipilimumab is not cost-effective compared with chemotherapy regimen in the first-line treatment of unresectable MPM. However ，if patients receive complimentary drugs ，the dual-immunotherapy regimen is cost-effective.