Daintain/allograft inflammatory factor-1 (AIF-1), as a novel inflammatory factor, has been reported to accelerate the proliferation and migration of breast cancer cells. However, the effect of daintain/AIF-1 on hepatocarcinogenesis remains unclear. In order to explore the effect of daintain/AIF-1 on the progression of hepatocellular carcinoma (HCC), enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR) were performed to examine the secretion and gene expression of (IGF)-1, IGF-2 and IGFBP-3. The expression of IGF-1R and its downstream targets was evaluated by western blotting. In addition, the proliferation and cell-cycle progression of HepG2 cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazolium bromide (MTT) and flow cytometric analysis. The results showed that HepG2 cells subjected to daintain/AIF-1 treatment revealed an obvious increase in the secretion of IGF-1 and IGF-2, and a reduction in the secretion of IGFBP-3. Moreover, daintain/AIF-1 accelerated the activation of IGF-1-induced IGF-1R and its downstream AKT signaling pathway, and subsequently promoted the activation of cyclin D1 pathway, thus accelerating the progression of the cell cycle and eventually promoting the proliferation of HepG2 cells. In conclusion, daintain/AIF-1 promoted the proliferation of HepG2 cells by accelerating the activation of IGF-1R and its downstream signaling pathway, which confirms that daintain/AIF-1 plays a crucial role in the development of HCC.