BACKGROUND It is unclear whether etoposide/cisplatin (EP) regimen is the optimal chemotherapy regimen in the treatment patients with extensive small cell lung cancer (SCLC), this study was aimed to evaluate the efficacy and safety of patients with extensive SCLC treated with irinotecan/cisplatin (IP) versus EP. METHODS We searched EMBASE, PubMed, the Cochrane Library, China journal full-text database (CJFD), Chinese scientific journal full-text database (CSJD), Chinese biomedicine literature database (CBM) for randomized controlled trials comparing IP with EP regimens. Two reviewers independently assessed the quality of included studies and extracted data. We analyzed the data using Review Manager (version 5.0). RESULTS Four randomized controlled trials totaling 1 180 patients were included. The results of meta analysis were as follows: there was no significant difference between IP regimen and EP regimens in one year survive rate (RR=1.22, 95%CI: 0.97-1.54), two year survive rate (RR=2.26, 95%CI: 0.46-11.21). There was significant difference between IP regimen and EP regimens in overall response rate (RR=1.13, 95%CI: 1.03-1.25), grade 3/4 neutropenia (RR=0.48, 95%CI: 0.34-0.69), thrombopenia (RR=0.23, 95%CI: 0.15-0.36), grade 3 anemia (RR=0.55, 95%CI: 0.40-0.77), grade 3/4 diarrhea (RR=9.56, 95%CI: 4.91-18.59), grade 3 nausea/vomiting (RR=1.70, 95%CI: 1.19-2.43). CONCLUSIONS There is no significant difference between IP group and EP group with regard to one year survive rate, two year survive rate, but IP regimen improves reponse rate. IP regimen has less hematologic & greater gastrointestinal toxicity compared with EP, EP regimen remain the main standard chemotherapy in the treatment extensive small cell lung cancer due to cheapness, they still need to be confirmed by randomized controlled trials.