To investigate the functional differences of angiopoietin-related protein 4 () transcripts in hepatocellular carcinoma (HCC) cells. By transfecting -Transcript 1 and -Transcript 3 overexpression vectors into HepG2 and Huh7 cell lines with knockdown, the effects of overexpression of two transcripts on cell viability, invasion, migration, and apoptosis were analyzed. The expression of two transcripts was compared in human liver cancer tissue, and their effects on tumor development were validated experiments in mice. Compared with control, the overexpression of -Transcript 1 had no significant effect on viability, invasion, healing, and apoptosis of HepG2 and Huh7 cells. However, these two cell lines overexpressing -Transcript 3 showed remarkably enhanced cell viability, invasive and healing ability, and decreased apoptosis ability. Furthermore, the mRNA level of -Transcript 3 was significantly increased in human HCC tissues and promoted tumor growth compared with Transcript 1. Different transcripts of gene have distinct effects on HCC. The abnormally elevated Transcript 3 with the specific ability of promoting HCC proliferation, infiltration, and migration is expected to become a new biological marker and more precise intervention target for HCC.