Small-cell lung cancer (SCLC) is a highly aggressive malignancy predominantly treated with chemotherapy or chemoradiotherapy. The role of surgical intervention in SCLC, however, remains inadequately defined. This study aimed to retrospectively analyze the clinical data of patients with SCLC who underwent surgical treatment to assess the impact of surgery combined with perioperative adjuvant therapy on long-term prognosis, with the goal of informing future treatment strategies.This study included patients with SCLC who underwent surgical treatment at West China Hospital, Sichuan University, between 2005 and 2021. Prognostic factors influencing overall survival (OS) and disease-free survival (DFS) were analyzed using univariate and multivariate Cox regression models, in conjunction with the Kaplan-Meier method.A cohort of 121 patients with SCLC who underwent surgical treatment was included. Multivariate Cox regression analysis indicated that postoperative adjuvant chemotherapy [hazard ratio (HR) =0.45; 95% confidence interval (CI): 0.24-0.85] was significantly associated with improved OS, whereas a smoking index exceeding 400 (HR =1.0011; 95% CI: 1.0004-1.0018) was identified as an independent adverse prognostic factor. Pathological stratification showed that prophylactic cranial irradiation (PCI) was significantly associated with improved OS in stage II/III patients (P<0.05) but had not in stage I patients (P>0.05). Regarding DFS, preoperative neoadjuvant chemotherapy was associated with significantly prolonged DFS (HR =0.44; 95% CI: 0.21-0.94), while lymph node metastasis was identified as a negative predictor (HR =1.97; 95% CI: 1.16-3.36).Surgical intervention combined with perioperative adjuvant therapy provides significant survival benefits for patients with SCLC. Notably, preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy were associated with prolonged DFS and OS. For early-stage patients, the application of PCI should be approached cautiously. Further prospective studies are warranted to better balance its potential risks and benefits.Copyright © 2025 AME Publishing Company. All rights reserved.