Background: Immune checkpoint inhibitor monotherapy has emerged as a breakthrough therapy in the treatment of various cancer. However, programmed cell death (PD-1) inhibitors alone as secondary line treatment yield uncertain response in liver cancer in different studies. Despite encouraging preclinical findings that radiation primes the immune system and produces a synergistic anti-tumor immunity for durable disease control, few clinical data is published so far. To investigate the efficacy and safety of the combination of radiation and PD-1 inhibitors in metastatic and recurrent liver cancer, we proposed this study. Methods: Patients diagnosed with stage IV (American Joint Committee on Cancer Staging System 8th) or recurrent liver cancer, received radiotherapy followed by PD-1 inhibitors or concurrent radiation and PD-1 inhibitors were enrolled. Data regarding clinicopathologic characteristics, treatment protocols, response rates, toxicities, and survival were collected. Survivals were calculated from the date of the first delivery of immunotherapy using Kaplan-Meier method. Results: From April 2017 to December 2020, 34 patients were eligible. Twenty-nine (85.3%) patients were male and 5(14.7%) were female. The median age was 58 years old. Twenty-three patients (67.6%) had hepatocellular carcinoma. Totally, radiotherapy was delivered to 92 lesions (28 liver, 28 venous tumor emboli, 13 lymph nodes, 18 bone, 5 others) of these patients. The radiation dose ranged from 40Gy to 60Gy (2-5Gy per fraction). Sixteen patients, 15 patients, 5 patients, 1 patient and 1 patient received toripalimab, sintilimab, camrelizumab, nivolumab and pembrolizumab, respectively (Four patients received multiple- drugs in different time ). PD-1 inhibitors were administered very 3 weeks until progression or limiting toxicities. After treatment, 3,18 and 11 patients achieved complete response, partial response and stable disease. The response rate and disease control rate were 61.8% and 94.1%, respectively. Grade 3 adverse events were observed in 11 patients (32.4%), including 6 patients with thrombocytopenia (2 with grade 4, 4 with grade 3), 2 patients with gastrointestinal events and 3 with others. No grade 5 adverse event was recorded. The median follow up time was 16.5 months. The median overall survival (OS) time and progression free survival (PFS) time were 15.4 months and 11.3 months. One-year OS and PFS were 62.9% and 46.5%, respectively. Two-year OS and PFS were 31.8% and 11.3%, respectively. Conclusions: The combination of immunotherapy and radiotherapy was safe and tolerable. The application of radiation before or during PD-1 inhibitors delivery fostered the immune response and enhance the efficacy of immunotherapy with prolonged PFS and OS in recurrent and metastatic liver cancer. A phase II prospective trial is ongoing.