Abstract: Acute Hepatopancreatic Necrosis Disease (AHPND) is an important limiting factor affecting the healthy cultivation of shrimp in recent years, which has brought huge economic losses to the global shrimp industry. In order to explore the relationship between the occurrence of AHPND and environment, pathogen and shrimp immunity factors, the pond cultured Litopenaeus vannamei systems were continuously monitored. Based on the 35 days continuously monitoring showed that, the air temperature, water temperature, dissolved oxygen (DO), pH, salinity, ammonia nitrogen (NH₄-N) and nitrite (NO₂-N) were fluctuated in the range of 21—29℃, 24.8—31℃, 1.4—8.32 mg/L, 8—8.91, 34—50, 0.01—0.26 mg/L and 0.005—0.212 mg/L, respectively; the culturable bacteria and Vibrio sp. in water and shrimp hepatopancreas were fluctuated in the range of 3×10³—2.4×10⁵ CFU/mL, 2×10²—1.8×10⁴ CFU/mL, 9.8×10⁴—8.8×10⁶ and 3.9×10³—3.61×10⁶ CFU/g, respectively; 135 isolates of Vibrio sp. were detected based on 16S rDNA, and the main Vibrio species was V. owensii, V. campbellii, V. parahaemolyticus, V. alginolyticus and V. harveyi; the activities of ACP, AKP, SOD, LZM and PO were 7.5—75, 1.0—8.5, 2.4—11.07, 1.3—43 and 23—28 U/mg, respectively. Combined the physical and chemical factors before and after the occurrence of AHPND, the results showed that, water temperature, culturable bacteria and Vibrio sp. in hepatopancreas, DO, LZM and PO could be used as the early warning candidate factors for the occurrence of AHPND in pond culture. The results provide a scientific basis for the healthy culture of L. vannamei and the prevention and control of AHPND disease.