Enhanced cell migration and invasion play key roles in cancer metastasis. However, the molecules involved in this process are not fully understood. In this study, a full-length human BNIPL-2 (Bcl-2/adenovirus E1B 19 kDa interacting protein 2 like-2) cDNA was transfected into human hepatocellular carcinoma cells with low metastatic potential (MHCC97-L). The in vitro and in vivo effects of BNIPL-2 on cell invasion and metastasis were examined. In vitro analysis showed that the overexpression of BNIPL-2 increases cell invasion and promotes cell migration. The rates of intrahepatic and pulmonary metastasis in nude mice were also increased. Cdc42 activation assays and immunoblot analysis indicated that the activation of Cdc42 and the upregulation of CD44 were involved in the metastasis of cancer cells. The overexpression of BNIPL-2 promotes the invasion and metastasis of MHCC97-L cells. Thus, BNIPL-2 is a gene related with cancer metastasis.