Jujube honey, a very popular honey in China, has been shown to own numerous biological properties. However, the anticancer effect and the underlying mechanisms of jujube honey in HepG2 cells have not been investigated to date. This study was designed to evaluate jujube honey-induced apoptosis and its molecular mechanism in HepG2 and the following results were obtained. Firstly, treatment with jujube honey blocked cell cycle progression at the G0/G1 phase, reduced the mitochondrial membrane potential (Delta psi m), induced DNA damage, and upregulates p53 expression. Secondly, pro-apoptotic proteins Bax and Bad were upregulated and antiapoptotic proteins Bcl-2 and Bcl-xL were downregulated. Lastly, caspase activation and apoptotic death occurred in HepG2 cells. In conclusion, this study showed that jujube honey induces HepG2 cell apoptosis via DNA damage, p53 expression, and caspase activation. Practical applications We demonstrate the molecular mechanism by which jujube honey triggers apoptosis in HepG2 cells. This new insight provided useful information on the use of jujube honey as a potential therapeutic and preventive agent.