Esculetin is a coumarin compound with anticancer, antioxidant, and anti-inflammatory activities. In this study, we synthesized an esculetin derivative, 6,7-bis(Pentyloxy)-2H-Chromen-2-One (BPCO), through etherification. BPCO inhibited the proliferation of HepG2 cells in a dose- and time-dependent manner. It also inhibited cell migration, promoted apoptosis, and caused cell cycle arrest at the G1 phase. Additionally, BPCO downregulated the expression levels of Bcl-2 and Bcl-XL and upregulated the expression levels of Bax and Bak. This study shows that BPCO inhibits hepatocellular carcinoma cell proliferation and induces apoptosis, providing a basis for further study of BPCO as an antitumor agent.