Objective To explore the role and safety of ozone water administered through hepatic artery infusion in rabbits with VX2 liver cancer.Methods A VX2 liver cancer model was established in New Zealand white rabbits, which were randomly divided into the ozone water group (n=20) and the saline group (n=20), and underwent surgical intervention. Blood samples were collected from the ear vein 1 day before surgery and on postoperative days 1, 3, and 5 to measure AST, ALT, Cr, TNF-α, IL-6, and IL-1β. CT scans were performed on postoperative days 7 and 14 to calculate tumor volume growth rates. Pathological examination was conducted on day 28 post-surgery. Results Ozone administered through hepatic artery infusion inhibited tumor cell growth, promoted tumor cell necrosis, and increased the release of TNF-α, IL-6, and IL-1β in VX2 liver cancer in rabbits. There was no significant impact on liver and kidney function in the tumor-bearing rabbits. Conclusion This study confirms that ozone water administered via hepatic artery infusion in VX2 liver cancer-bearing rabbits is an effective and safe approach, warranting further research and exploration