In this study, we investigated the protective effect of an Alcalase enzymatic hydrolysate derived from Batillus cornutus meat (BMA) against hydrogen peroxide (H2O2)-induced oxidative damages in hepatocytes. First, we confirmed that BMA containing plentiful taurine has the antioxidant activities by scavenging 2,2-azino-bis (3-ethylbenzthiazoline)- 6-sulfonic acid radical (ABTS+) and increasing the reducing power and oxygen radical absorbance capacity (ORAC) value. Also, the treatment of BMA increased the cell viability by reducing the intracellular reactive oxygen species (ROS) production in H2O2-stimulated hepatocytes. In addition, BMA effectively decreased the sub-G1 DNA contents and the apoptotic body formation increased by H2O2 stimulation via modulating the protein expression levels of apoptotic molecules (Bcl-2, Bax and p53). Moreover, BMA suppressed the activation of extracellular signal-regulated kinase (ERK)/p38 and nuclear factor (NF)κB signaling by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling known as antioxidant systems in H2O2-stimulated hepatocytes. These results suggest BMA protects hepatocytes against oxidative damages caused by H2O2 stimulation.