Objective: To analyze the clinical efficacy and safety of Sintilimab combined with albumin-bound paclitaxel and platinum-based chemotherapy in the treatment of locally advanced lung cancer. Methods: This study enrolled 64 patients with locally advanced lung cancer from March 2022 to March 2025. According to random number table method, they were divided into standard group (albumin-paclitaxel + platinum-based chemotherapy regimen) and combined group (sintilimab combined with albumin-paclitaxel + platinum-based chemotherapy regimen), 32 cases in each group. All patients were continuously treated for 12 weeks. The clinical curative effect [objective response rate (ORR), disease control rate (DCR)], tumor markers [serum squamous cell carcinoma antigen (SCC), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA)], adverse reactions and progression-free survival (PFS) were compared between the two groups. Results: The combination group showed significantly superior ORR and DCR relative to the standard group (P<0.05). Following treatment, levels of SCC, CYFRA21-1, and CEA decreased in both groups, with the combination group exhibiting lower values than the standard group (P<0.05). During treatment, there was no significant difference in the occurrence of adverse reactions (gastrointestinal reactions, immunosuppression, abnormal liver function, sexual immune-related pneumonia, peripheral neurotoxicity) between the two groups (P>0.05). PFS in combined group was longer than that in standard group (P<0.05). Conclusion: Sintilimab combined with albumin-paclitaxel + platinum-based chemotherapy regimen can increase tumor response rate and disease control rate, reduce levels of tumor markers and prolong progression-free survival in locally advanced lung cancer, which has good safety.