--- - |2 Summary The circulating miRNAs are dysregulated in non‐small cell lung cancer (NSCLC) and have great promise for clinical diagnosis. The aim of this study was to screen and evaluate the reliability and diagnostic efficiency of candidate serum miRNAs for NSCLC diagnosis. We found that miR‐21 and let‐7a were significantly dysregulated in NSCLC patients (P < .001). When applied for NSCLC diagnosis, combined application of miR‐21 and let‐7a had a sensitivity of 0.790, specificity of 0.750, which is significantly higher than application alone of miR‐21(sensitivity 0.647; specificity 0.641), let‐7a (sensitivity 0.653; specificity 0.718) or computed tomography‐guided core‐needle biopsy (CTCB) (sensitivity 0.725; specificity 0.609) (P < .01). In conclusion, our study indicates that combined application of circulating miR‐21 and let‐7a has advantages over traditional CTCB technique. - Clinical and Experimental Pharmacology and Physiology, Volume 45, Issue 10, Page 1083-1086, October 2018.