Objective: To investigate the effects of DEHP exposure on PI3K/AKT signaling pathway and HCAECs, and to provide a theoretical basis for the treatment of HCAECs damaged by DEHP exposure. Methods: According to relevant literature research, HCAECs were treated with different concentrations of DEHP and divided into control group (DMSO) and experimental group (DEHP 128, 256, 384, 512 μM). The ability of cell proliferation was measured by CCK- 8 assay, the ability of cell tube formation was evaluated by in vitro tube formation assay, the level of apoptosis was evaluated by flow cytometry, and the levels of P-PI3K, PI3K, P-AKT, AKT and apoptosis-related proteins BAX, Bcl-2, cleaved caspase-3 and caspase-3 were detected by Western-Blot. Results: CCK-8 assay showed that DEHP inhibited the proliferation ability of HCAECs in a concentration- and time-dependent manner (p<0.05). The results of in vitro tube formation assay showed that the morphology of cells in the experimental group was mostly isolated round and oval. The number of intersections formed was reduced compared with the control group (p<0.05) when the DEHP concentration was ≥256 μM. The results of flow cytometry showed that the proportion of apoptosis in the experimental group was higher than that in the control group (p<0.05). Western-blot results showed that the expression level of Bcl-2 in the experimental group was lower than that in the control group, while the levels of BAX and cleaved caspase-3/caspase-3 increased (p<0.05). And the ratio of P-PI3K/PI3K and P-AKT/AKT were lower than those in the control group (p<0.05) when DEHP≥256μM. Conclusion: DEHP can induce apoptosis and inhibit the proliferation and angiogenesis of HCAECs by inhibiting PI3K/AKT/ signal pathway.