Objective To observe the impact of the prophylactic cranial irradiation (PCI) and its different interventional times on the prognosis of patients with limited-stage small cell lung cancer (LSCLC) who received comprehensive therapy of complete response (CR). Methods A total of 184 LSCLC patients who received radiotherapy and chemotherapy based on comprehensive treatment were retrospectively analyzed. Patients were divided into two groups based on with or without PCI intervention. There were 50 patients (27.2%) in the PCI group and 134 patients (72.8%) in the non PCI group. The PCI group was subdivided into two groups, PCI1 group (n=20) and PCI2 group (n=30), according to whether patients completed 4 cycles of chemotherapy. Chemotherapy regimen, irradiation method and dose were identical for two groups. Results The brain metastasis rates were 14.0%and 30.6%for PCI group and non PCI group. There was significant difference in brain metastasis rate between the two groups (P<0.05). The median survival times were 25 months (95%CI:21.487-28.513) and 17 months (95%CI:15.175-18.825) for PCI group and non PCI group (P<0.05). The 1, 2 and 3-year survival rates were 54%, 36%, 15% and 37%, 18%, 13% for the two groups. There were no significant differences in brain metastasis rates between PCI1 group and PCI2 group (10.0% and 16.7%). There was no significant difference in median survival time between the two subgroups. Conclusion PCI can reduce the incidence of SCLC brain metastases, and prolong the overall survival time. However, different intervention times of PCI have no significant influence on the prognosis of LSCLC.