To evaluate whether the systemic inflammation score (SIS) could predict postoperative outcomes for patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for early-stage non-small-cell lung cancer (NSCLC). This retrospective study was conducted on the prospectively maintained database in our institution between January 2016 and December 2017. Preoperative SIS comprising serum albumin (sALB) and lymphocyte-to-monocyte ratio (LMR) was graded into 0, 1 and 2, and then utilized to distinguish patients at high surgical risks. Multivariable logistic-regression analysis was conducted to determine independent risk factors for postoperative outcomes. There were 1,025 patients with TNM-stage I-II NSCLC included, with an overall morbidity rate of 31.1% and mortality rate of 0.3%. We applied the sALB at 40 g/L and the median LMR of our series at 4.42 as dichotomized cutoffs for modified SIS scoring criteria. Both minor and major morbidity rates in patients with SIS=2 were significantly higher than those in patients with SIS=0 and with SIS=1 (P<0.001). No difference was found in overall morbidity rate between patients with SIS=1 and with SIS=0 (P=0.20). No significant difference was found in the mortality rate between these 3 groups. Patients with SIS=2 had the highest probability to experience most of individual complications. Finally, multivariable logistic-regression analysis suggested that preoperative SIS=2 could independently predict the morbidity risks following VATS lobectomy (OR=1.73; 95% CI=1.11-2.71; P=0.016). The SIS scoring system can be employed as a simplified, effective and routinely operated risk stratification tool in patients undergoing VATS lobectomy.