Palm oil extract (POE) at different concentrations (0.1–500 µg/mL) was evaluated for antioxidant and antihepatoma activities. Results showed that POE exhibited a greater antioxidant activity than α-tocopherol in all model systems tested. At concentrations of 0.1–100 µg/mL, POE showed a superoxide radical scavenging activity ranging from 50.6 to 100%, with an IC50 value (0.09 µg/mL) lower than α-tocopherol (0.51 µg/mL). In the xanthine oxidase inhibition test, POE (IC50 = 0.67 µg/mL) also exhibited a stronger inhibitory effect on xanthine oxidase activity than α-tocopherol (IC50 = 0.83 µg/mL). At concentrations of 0.1 µg/mL and above, POE showed significant ability in inhibiting the oxidative damage to lipids induced by ascorbate-Fe2+ than α-tocopherol in rat liver (IC50 = 0.53 µg/mL versus 0.94 µg/mL), brain (IC50 = 0.10 µg/mL versus 52.52 µg/mL) and plasma (IC50 = 77.17 µg/mL versus 190.81 µg/mL). In the antihepatoma studies, POE showed a greater potency than α-tocopherol in inhibiting Hep G2, Hep 3B and PLC/PRF/5 cells. The antiproliferative effect of POE against these human hepatoma cells was dose-dependent, with IC50 values varying from 4.86 to 68.44 µg/mL. The present results demonstrate that POE is an effective natural antioxidant supplement for protecting cellular membranes against oxidative damage and inhibiting hepatoma cell proliferation.