OBJECTIVE: Malignant mesothelioma (MM) is a rare malignant tumor. To explore the clinicopathological characteristics and efficacy of Chinese population with MM in the real-world. METHODS: Two hundred and forty-eight patients diagnosed with MM between September 2007 and August 2024 from three large medical centers (Beijing Hospital, Peking University Cancer Hospital, and Chinese Academy of Medical Sciences Cancer Hospital) were retrospectively analyzed. Kaplan-Meier and Cox regression were performed. Breast cancer gene 1-associated protein 1 (BAP1) status was evaluated. RESULTS: Chinese population with MM had a lower diagnostic age, higher proportion of youth and female, more advanced stage and lower expression of characteristic markers. The median progression-free survival (mPFS) and median overall survival (mOS) were 8.90 and 25.60 months for the first-line treatment, and 3.28 and 19.50 months for the second-line. The first-line immunotherapy provided a relatively higher objective response rate (33.3% vs. 20.5%, p = 0.402) and a trend to prolong mPFS (12.10 vs. 9.20 months, p = 0.345) and mOS (NA vs. 23.90, p = 0.185) compared with chemotherapy. Bevacizumab combined with chemotherapy relatively prolonged mPFS (10.47 vs. 7.93 months, p = 0.074) and mOS (31.30 vs. 23.20 months, p = 0.673) than chemotherapy alone. Carboplatin relatively improved mPFS than cisplatin (10.87 vs. 8.87 months, p = 0.185). Age and histologic type were predictors for PFS, and gender, histologic subtype, and CK5/6 were prognosis factors for OS. Briefly, 17.78% patients existed BAP1 deletions and correlated with OS benefit. CONCLUSION: Chinese population with MM present unique clinicopathologic characteristics and could benefit from the first-line immunotherapy and bevacizumab combined with chemotherapy. Gender, histologic subtype, and CK5/6 are prognosis factors for OS. BAP1 deletions correlate with OS benefit.