Chronic lymphocytic leukemia (CLL) is known as the most common lymphoid malignancy in the Western world. MicroRNAs (miRNAs) are a class of small noncoding RNAs with pivotal roles in cellular and molecular processes related to different malignancies including CLL. Recently, some studies have shown that miR-192 plays a key role in CLL pathogenesis through increasing CDKN1A/p21 levels, suppression of Bcl-2 and enhancement of wild-type P53 and cell cycle arrest. Forty samples, including 20 patients with CLL, diagnosed in Omid hospital (Isfahan, Iran) and 20 healthy controls were sampled during a period of 4 months. Using real-time PCR method, expression of miR-192 was analyzed in peripheral blood mononuclear cells (PBMCs) of CLL patients in comparison with healthy subjects. In silico molecular signaling pathway enrichment analysis was also performed on validated and predicted targets (targetome) of miR-192 in DAVID database to explore possible role of miR-192 in some pathways. The expression of miR-192 was found to be significantly reduced (˜2.5-folds) in CLL patients compared with healthy subjects (P = 0.002). In silico molecular signaling pathway enrichment analysis detected cell indicated signaling pathway as one of the most statistically relevant pathway with miR-192 targetome. Our findings showed that miR-192 could be a biomarker for early diagnosis of CLL.