Introduction: In the search of new therapeutical strategies against non-small-cell lung cancer (NSCLC), the identification of new prognostic factors is crucial. Objectives: In this study, we analyzed the prognostic value of the liver X receptor-alpha (LXR-alpha), a nuclear receptor of a family of cholesterol derivatives called oxysterols, in patients with radically resected NSCLC. Methods: We retrospectively reviewed 140 stage II and III surgically treated NSCLC patients that were grouped by percentage of LXR-alpha-positive cells value above or below its median value. Tumor-related survival was evaluated as primary end point. Results: The 5-year overall and tumor-related survival rates were 40% and 46%, respectively. The median percentage of LXR-alpha-positive cells was 20%. Patients with stage II NSCLC had higher LXR-alpha values than those with stage III (P=.04). Univariate analysis demonstrated that both TNM stage and LXR-alpha were significantly related to tumor-related survival (P=.006 and P=.004, respectively). The 5-year tumor-related survival rates in stage II and III NSCLC were 56% and 34%, respectively. The 5-year tumor-related survival rates in high and low LXR-alpha value were 57% and 32%, respectively. The multivariate analysis showed that both TNM stage and LXR-alpha were independent prognostic factors (P=.01 and P=.007, respectively) with hazard ratio of 1.92 and 0.49, respectively. Conclusion: LXR-alpha seems to be an independent prognostic factor indicating a better survival in completely resected stage II and III NSCLC patients. © 2016 John Wiley & Sons Ltd.