BackgroundEGFR‐mutant (EGFR‐M) and ALK‐positive (ALK‐P)are common in malignant pleural effusion (MPE) with metastatic non‐small‐cell lung cancer (NSCLC) (MPE‐NSCLC). The impact of thoracic tumor radiotherapy on survival in such patients remains unclear. We aimed to investigate whether thoracic tumor radiotherapy could improve overall survival (OS) in such patients.MethodsAccording to whether or not patients accepted thoracic tumor radiotherapy, 148 patients with EGFR‐M or ALK‐P MPE‐NSCLC treated with targeted therapy were classified into two groups: DT group without thoracic tumor radiotherapy and DRT group with thoracic tumor radiotherapy. Propensity score matching (PSM) was performed to balance clinical baseline characteristics. Overall survival was analyzed by Kaplan–Meier, compared by log‐rank test, and evaluated using Cox proportional hazards model.ResultsMedian survival time (MST) was 25 months versus 17 months in the DRT group and DT group. The OS rates at 1, 2, 3, 5 years in the DRT group and DT group were 75.0%, 52.8%, 26.8%, 11.1% and 64.5%, 28.4%, 9.2%, 1.8%, respectively (χ2 = 12.028, p = 0.001). Compared with DT group, the DRT group still had better survival after PSM (p = 0.007). Before and after PSM, factors associated with better OS through multivariable analysis were that thoracic tumor radiotherapy, radiotherapy, N0‐2, and ALK‐TKIs. Grades 4–5 radiation toxicities were not observed in patients; 8 (11.6%) and 7 (10.1%) out of the DRT group suffered from Grade 3 radiation esophagitis and radiation pneumonitis, respectively.ConclusionOur results for EGFR‐M or ALK‐P MPE‐NSCLC showed that thoracic tumor radiotherapy may be crucial factor in improving OS with acceptable toxicities. Potential biases should not be neglected: Further randomized controlled trials are necessary to confirm this result.