Introduction and Objective: For the treatment of cancers, various methods are employed, including surgery, chemotherapy, radiotherapy, immunotherapy, and targeted therapy. The results of these treatments vary depending on the stage of cancer and the patient's condition. Recently, treatment through microRNAs has begun due to their key role in regulating gene expression and influencing biological processes related to cancer. This novel approach has high potential for controlling tumor growth and early cancer detection. MicroRNAs play an important role in regulating gene expression and can act as either oncogenes or tumor suppressors. miR-181a acts as an oncogene in gastric and colorectal cancers, playing a role in tumorigenesis. Increased expression of this microRNA is associated with tumor progression, metastasis, and lower survival rates in patients. Given that miR-181a is involved in various types of cancers, this research could help better understand this microRNA in other cancers such as liver cancer and pave the way for the development of new therapies. Overall, miR-181a is one of the key microRNAs in cancers that could be considered a new therapeutic target. The use of antisense oligonucleotides as a powerful tool in genetic engineering and disease treatment, especially cancer, has attracted researchers' attention. In this study, we investigated the role of microRNA-181a in the pathogenesis of hepatocellular carcinoma (HCC). By using anti-miR-181a, we aimed to inhibit the expression of miR-181a in HepG2 cells, which not only reduces RNAi activity but may also have positive effects on controlling cancer cell growth. Additionally, we identified target genes of miR-181a and proposed a hypothesis that these genes play a significant role in reducing tumor growth and cancer progression by regulating specific signaling pathways. The results of this research could serve as a starting point for developing innovative therapeutic strategies based on microRNAs for the trea