KRAS mutation is one of the most common driver oncogenes in non-small cell lung cancer (NSCLC), and the most common mutation subtype is G12C. However, there is still a lack of efficacy and prognosis data related to immunotherapy, which hinders the promotion of new strategies.Clinical characteristics and treatment outcomes were collected and analyzed for patients with NSCLC harboring KRAS mutations at West China Hospital of Sichuan University from June 2013 to March 2023.Among the 231 patients with KRAS-mutated NSCLC, 29.4% had KRAS G12C mutations. Compared to the KRAS non-G12C NSCLC group, the KRAS G12C NSCLC group had a greater number of pack-years. The programmed death ligand 1 expression and the proportion of patients with a high tumor mutational burden were not significantly different between the two groups. Similar patterns of TP53, STK11, and CDKN2A mutations were observed between KRAS G12C and KRAS non-G12C NSCLC groups. The median progression-free survival (PFS) (8.4 vs 7.0 months, p=0.100) and overall survival (OS) (12.1 vs 18.1 months, p=0.590) were not statistically different between KRAS G12C and KRAS non-G12C. Compared to patients with KRAS G12C NSCLC who did not receive immunotherapy, patients who received immunotherapy had a better objective response rate (46.2% vs 0%, p=0.002), PFS (12.2 vs 7.5 months, p=0.087) and OS (49.9 vs 11.1 months, p=0.12).Patients with KRAS G12C were more likely to be smokers. Advanced KRAS G12C NSCLC patients who received immunotherapy had a better ORR than those who did not, suggesting that patients with G12C mutations are more likely to benefit from immunotherapy.© 2024 Jing et al.