In order to explore the immune-regulation function of 6-Shogaol in fish, the growth rate, the production of intracellular reactive oxygen (ROS) and lipid peroxidation (MDA), antioxidant enzyme activity, and key genes expression in inflammatory and antioxidant pathways were detected in zebrafish liver cells incubated with different concentrations of 6-Shogaol for 48 h. The results showed that 6-Shogaol antioxidant effect was significant, with the highest activity of antioxidant enzyme SOD and GSH-PX, and lowest production of ROS AND MDA in 20 μmol /L treatment group (P<0.05), The mechanism of action might be due to the activation of Keap1-Nrf2/HO-1-antioxidant enzyme signaling pathway by inhibiting the keap1 expression (P<0.05). High concentrations of 6-Shogaol inhibited the proliferation of liver cells (P<0.05). 6-Shogaol increased the expression of inflammatory cytokine genes in NF-κB inflammatory pathway (tnf-α, il-1β, il-6) in zebrafish liver cells (P<0.05). While in contrast to the control group, 6-Shogaol down-regulated the anti-inflammatory cytokine il-10 expression. The above results showed that 6-Shogaol in the concentration of 20 μmol /L can promote the antioxidant function and the supplementation of 6-Shogaol can activate innate immune response in zebrafish liver cell.