miRNAs participate in the activation of PI3K/AKT signaling pathway by binding to the 3′-UTR of the targeted mRNAs, in particularly phosphatase, and tensin homolog (PTEN), which is a negative regulator in PI3K/AKT pathway, For example, miR-21, miR-222, miR-494, miR93, and miR153 are all proved inducers of sorafenib resistance in HCC cells by targeting PTEN (15, 16, 19, 31, 49). This evidence concerns the gene PTEN and hepatocellular carcinoma.