Background: Although systemic therapy is standard treatment for stage IV NSCLC, radiation therapy can also play an important role. In the practice of our institute, radiotherapy to local diseases has been extensively used. In this study, we observed and analyzed the outcomes of systemic therapy combined with radiotherapy in stage IV non-small cell lung cancer. Methods: Patients with stage IV non-small cell lung cancer treated with combination of systemic therapy and radiotherapy were enrolled in this study. Radiotherapy was delivered using sIMRT or VMAT technique with CBCT image guidance. SBRT or hypofractionated radiation was used according to lesion site and patients general condition. For patients with driving gene mutations TKIs were used, and for these without chemotherapy of cisplatin/carboplatin plus paclitaxel or pemetrexed was given. Results: From 2016 to 2018, 105 patients were included in this study. Sites mostly irradiated included pulmonary lesions or mediastinal lymph nodes(48%), intracranial metastatic lesions(33%), bone metastatic lesions (20%). 42% of all patients received one course of radiotherapy to a single lesion site and others received multiple courses of radiation to different sites. Median follow-up was 39.1 months. Median OS for whole cohort was 18.6 months. In subgroup analysis, the survival of TKIs+radiotherapy group as significantly better than that of chemotherapy+radiotherapy group (median OS: 35.2 months vs 11.1 months, p < 0.001). The survival of patients with oligometastasis was also significantly better than these with extensive diseases( median OS 25.3 months vs 7.9 months, p < 0.001). The local control rate of irradiated sites was 82%. The incidence of ≥Grade 2 radiation esophagitis and pneumonitis were 33.2% and 24.2% for thoracic radiotherapy. Conclusions: Radiotherapy combined with systemic therapy is feasible and well tolerated for stage IV NSCLC, especially for patients with driving gene mutations and oligometastasis. It needs to be further confirmed by large randomized controlled clinical studies.