PURPOSE: To evaluate the efficacy and safety of induction immunochemotherapy followed by hypo-fractionated radiotherapy (Hypo-RT) for locally advanced unresectable non-small cell lung cancer (LA-NSCLC). METHODS: This retrospective analysis involved the data of 35 patients with unresectable stage III LA-NSCLC receiving immunotherapy plus Hypo-RT from January 1, 2019, to December 31, 2023. At least 2 cycles of induction immunochemotherapy were initially administered, followed by a definitive Hypo-RT at 4 Gy per fraction. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS) and grade ≥ 3 nonhematologic toxicities. Time-to-event outcomes for the entire cohort were calculated using the Kaplan-Meier method. RESULTS: At a median follow-up of 31.5 months (95% confidence interval, 26.1 to 36.9 months), median OS did not reach, with 1, 2, and 3-year OS rates of 100.0%, 82.5%, and 77.3%, respectively. Disease progression or death was recorded in 18 (51.4%) patients, with a median PFS of 28.0 months (95% CI, 9.4 to 46.6 months). The 1, 2, and 3-year PFS rates were 74.3%, 55.7%, and 47.6%, respectively. CONCLUSION: Induction immunochemotherapy followed by Hypo-RT demonstrated promising efficacy and acceptable toxicity in patients with LA-NSCLC. Studies on Hypo-RT combined with induction and consolidation immunotherapies are warranted in the future.