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Background: Recent evidence underscores to the important regulatory roles of microRNAs as a biomarker for diagnosis of non-small cell lung cancer (NSCLC); this disease often has poor prognosis, and it is the most prevalent cause of cancerrelated mortality worldwide. This study investigated the levels of miR-146a-5p and miR-196a-2 in peripheral blood mononuclear cells (PBMC). Methods: In the present case-control research, we collected the PBMCs through isolating blood from 22 NSCLC patients and 22 healthy individuals. Following the extraction of total RNA and cDNA synthesis, we studied the expression levels of miR-146a and miR-196a-2 by using qPCR. Results: Both the miR-146a-5p and miR-196a-2 were significantly down-regulated in the PBMCs of NSCLC patients in comparison with normal healthy ones (P=0.002 and P<0.001, respectively). There was an association between the expression levels of microRNAs and the types of tumors, which was significant for miR-146a-5p (P=0.02). Furthermore, in NSCLC cases, a significant positive correlation existed between miR-196a-2 and miR-146a-5p expression levels (r=0.71, P=0.002). Conclusion: According to the study results, miR-146a-5p and miR-196a-2 that were down-regulated in the PBMCs of NSCLC patients might serve as potential biomarkers for diagnosis if confirmed in future studies. [ABSTRACT FROM AUTHOR]