BackgroundLung cancer prognosis is related to various factors; however, the comprehensive relationship between these factors, including microRNAs (miRNAs), and lung cancer prognosis has not been determined. Thus, the aim of this study was to identify the key factors associated with lung cancer prognosis. MethodsWe retrospectively analyzed prognosis and relevant factors in 216 non-small cell lung cancer (NSCLC) patients diagnosed from January 2008 to December 2014. Paraffin-embedded lung tissue samples were used to detect miRNA-21 and miRNA-155. Clinical information was collected, including tumor malignancy, tumor node metastasis (TNM) classification, pathological type, site of the original tumor, and lung involvement. The association between factors and overall survival was analyzed. A Cox proportional hazard model was used to perform univariate and multivariate analyses. ResultsAge at surgery (hazard ratio [HR]1.021, 95% confidence interval [CI]1.003-1.040), TNM stages II (HR3.858, 95% CI2.449-6.078) and III (HR3.099, 95% CI1.911-5.023), and miRNA-21 (HR1.002, 95% CI1.001-1.003) and miRNA-155 expression (HR1.131, 95% CI1.064-1.202) were independent prognostic factors in NSCLC patients. MiRNA-21 expression with TNM stages II (HR1.282, 95% CI1.197-1.372) and III (HR 1.247, 95% CI1.149-1.354) interacted to affect prognosis in NSCLC patients. ConclusionsOlder age, higher clinical TNM stage, and increased miRNA-21 and miRNA-155 expression in NSCLC tissue were independently associated with poor survival in NSCLC patients. MiRNA-21 expression and clinical TNM stage interacted to affect prognosis.