The hypoxia conditions in intensive farming systems generate oxidative stress related to oxidative damage and mortality of fish. Corn husk meal (CHM), as a source of antioxidants, might modulate the antioxidant response and prevent the damage elicited by hypoxia. This study evaluated CHM’s ability to modulate a hepatic response in Nile tilapia exposed to hypoxia. A control and a test diet supplemented with 25 g CHM/kg feed were formulated. Ninety Nile tilapias (5.09 ± 0.55 g initial weight) were fed for 36 days to evaluate growth, feed efficiency, and hepatic antioxidant response (CAT, catalase; SOD, superoxide dismutase, and GPx, glutathione peroxidase) in normal oxygen conditions (normoxia). After the feeding trial (36 days), fish were exposed to hypoxia (1.5 ± 0.2 mg/L dissolved oxygen), and the hepatic antioxidant response was determined. There was no significant effect of CHM on growth and feed efficiency. The CAT activity was significantly increased in tilapias exposed to hypoxia and fed the test diet compared to the control group exposed to hypoxia. The SOD and GPx activities were unchanged in tilapias in normoxia and hypoxia conditions. Results suggest that CHM dietary supplementation promotes the antioxidant response in Nile tilapia exposed to hypoxia through CAT modulation.