Background: Single-agent immunotherapy is the standard second-line treatment of advanced esophageal cancer, however, the efficiency of single-agent immunotherapy is low, about 10-30%. Synergistic effects of radiation and immunotherapy have been demonstrated. This study evaluated the efficacy and safety of late-line immunotherapy combined with radiotherapy in patients with advanced esophageal cancer. Methods: We conducted a retrospective analysis of 85 patients treated at West China Hospital of Sichuan University between 2019 and 2022, all of whom had stage IV esophageal cancer and were treated with immunotherapy as a late-line therapy. We used Kaplan-Meier analysis to calculate progression-free survival (PFS), overall survival (OS). Results: After analysis, there were no differences in the baseline clinical characteristics such as age, gender, ECOG score, tumor location, and TNM stage. However, the proportion of received chemotherapy or targeted therapy may be greater in the non-radiotherapy group.38 were in the radiotherapy (RT) group and received radiotherapy to 41 lesion sites, and 47 were in the non-radiotherapy(non-RT) group. The most frequent radiotherapy organ sites were lymph nodes (14/41), esophagus (11/41), lung (9/41), bone (5/41), and brain (2/41) (three patients had irradiated metastases in two locations). The most common type of RT is conventional radiation therapy (31/41), including 12 radiotherapy courses of radical dose (50-60Gy, 28-30 fractions) and 18 radiotherapy courses of palliative dose (9-45Gy, 3-23 fractions). Then stereotactic body radiotherapy (10/41), (24-45Gy, 3-5 fractions). K-M analysis showed a median PFS in the RT group (16.7 months [95% CI 11.70-21.71 months]) vs. (6.97 months [95% CI 3.81-10.12 months], P = 0.014) in the non-RT group. And the median OS for the RT group was 24.4 months [95% CI 16.28-32.52 months] compared with 17.47 months [95% CI 15.11-19.83 months] (P = 0.039) for the non-RT group. The ORR of the RT group was 29.7% [95% CI, 14.3–45.2%] and 8.3% [95% CI, 2–16.4%] in the non-RT group(p=0.01). Univariate and multivariate analyses show that RT was an independent prognostic factor for OS. Overall, 33.3% and 32.5% of patients in the RT and non-RT groups, respectively, experienced at least one grade 3-4 treatment-related adverse event, with the most common treatment-related adverse reaction being myelosuppression, no differences in adverse effects between groups. Conclusions: In this study, late-line immunotherapy combined with radiotherapy for advanced esophageal cancer can improve the objective response rate and survival with manageable side effects. Although the limitations of retrospective studies should be taken into account, the findings still suggest that patients benefit from immunotherapy combined with radiotherapy, and more data are needed to assess the impact of radiation therapy on these patients.