In the current study, we addressed how and whether midkine is directly involved in resistance of CTCs to anoikis, and found that midkine plays an important role in enhancement of HCC cell resistance to anoikis, which was further demonstrated by an increased level of Bcl-2 and TrkB expressions and a decreased level of Bax and cleaved caspase-3 expressions as well as caspase-3 enzymatic activity. This evidence concerns the gene CASP3 and hepatocellular carcinoma.