Acute hepatopancreatic necrosis disease (AHPND) is the major bacterial disease of cultured shrimps, mainly caused by Vibrio parahaemolyticus associated with acute hepatopancreatic necrosis disease (Vp_AHPND). The aim of this study was to explore the anti-AHPND effect and its mechanism of immunoglobulin of yolk (IgY). Different doses of Vp_AHPND IgY agent (0, 0.2% and 0.5%) were added to shrimp feeds and immunized the juvenile L. vannamei for 28 d. The growth rate and survival rate of the juveniles, the activity of immune enzymes and the relative expression level of immune genes in shrimp hepatopancreas were measured. The resistance to Vp_AHPND infection of immunized juveniles was determined by the immersion infection. The growth experiment results showed that after 28 d of immunization, there was no significant difference in the average growth rate, specific growth rate and survival rate of the juveniles between the immunized group and the control group. The immune function test results showed that after 14 d of immunization, compared with the control group, the 0.2% immunized group (0.2% IgY agent) generated significantly higher enzyme activities for phenoloxidase (PO), superoxide dismutase (SOD) and lysozyme in the hepatopancreas. The relative expression level of antibacterial peptide (Crustin) gene was also significantly increased, while the relative expression level of β-1,3-glucan binding protein-lipoprotein (β-GBP-HDL) gene was significantly reduced in the 0.2% IgY agent group. The results of the immersion infection showed that the survival rate of the juveniles in the 0.2% IgY agent group was significantly higher than that of the control group, and the relative percentage of survival (RPS) of 0.2% IgY agent was 63.77%. In conclusion, oral administration of Vp_AHPND IgY agent will not adversely affect the growth and survival of L. vannamei. The 0.2% IgY agent can significantly enhance the immune function of L. vannamei by increasing the enzyme activities of PO, SOD, LZM and the expression level of Crustin gene, thereby improving the ability of shrimps to resist Vp_AHPND infection. This study implied that Vp_AHPND IgY agent has a strong application potential for the prevention of AHPND.