Abstract: Objective To compare the safety and efficacy of irinotecan combined with cisplatin chemotherapy(IP)and paclitaxel combined with cisplatin chemotherapy(TP)in second-line treatments for patients with relapsed and refractory small cell lung cancer. Methods A total of 53 patients with relapsed and refractory small cell lung cancer were randomly divided into IP group(n=29)and TP group(n=24), and the short-term and long-term efficacy and adverse reactions of the two groups were compared. Results The median progression-free survival time(PFS)of the IP group and the TP group were 4.5 months and 3.5 months, and the median overall survival time(OS)was 10 months and 9 months, respectively, and there were no significant differences between the two groups(P>0.05). Physical status(PS)score before receiving second-line treatment was an independent prognostic factor of PFS with irinotecan or paclitaxel combined with cisplatin chemotherapy(P<0.05); PS score before receiving second-line treatment and bone metastasis were independent prognostic factors of survival time(OS). The incidence of delayed-onset diarrhea in the IP group was significantly higher than that in the TP group(P<0.05). The incidence rates of numbness and joint pain in the TP group were significantly higher than that in the IP group(P<0.05). Conclusion Cisplatin combined with irinotecan or paclitaxel have similar efficacy and similar safety.