Background To evaluate the efficacy and safety of an immune checkpoint inhibitor (ICI) combined with chemotherapy in patients with advanced SCLC. Methods We searched published randomized-controlled trials (RCTs) to compare the effect of ICIs combined with chemotherapy and chemotherapy alone on SCLC. The extracted data included the number of people who achieved an objective response rate (ORR), the disease control rate (DCR), the hazard ratio (HR) of progression-free survival (PFS), and the overall survival (OS) with 95% confidence intervals (95% CI). Results Six RCTs involving 2477 patients were included. Compared with chemotherapy alone, patients receiving an ICI combined with chemotherapy had a significantly longer PFS (HR, 0.91; 95% CI 0.88-0.95,p < 0.00001) and OS (HR 0.92; 95% CI 0.89-0.96,p = 0.0001). The ORR increased, but the difference was not statistically significant (RR 1.05; 95% CI 0.99-1.12,p = 0.13). There was no significant difference in the DCR between the two treatment regimens; however, in patients treated with an ICI, fatigue, rashes, diarrhea, and elevated aminotransferase enzymes were significantly increased (p < 0.05). Conclusion ICI combined with chemotherapy is superior to chemotherapy alone with respect to PFS and OS in patients with advanced SCLC.