To determine the response of Litopenaeus vannamei to periodical salinity fluctuation, a 30-day experiment was conducted in laboratory. In this experiment, two salinity fluctuation amplitudes of 4(group S4) and 10(group S10) were designed. The constant salinity of 30(group S0) was used as the control. Levels of shrimp growth, molting frequency(MF), cellular energy status(ATP, ADP and AMP), as well as the expression of genes encoding molt-inhibiting hormone(MIH), crustacean hyperglycemic hormone(CHH), ecdysteroid-regulated protein(ERP), and energy-related AMP-activated protein kinase(AMPK) were determined. The results showed that periodical salinity fluctuation significantly influenced all indicators except MF which ranged from 13.3% in group S10 to15.4% in group S4. In comparison with shrimps cultured at the constant salinity of 30, those in group S4 showed a significant elevation in growth rate, food conversion efficiency, cellular energy status, ERP and MIH gene transcript abundance, and a significant reduction in CHH and AMPK transcript abundance(P < 0.05). However, salinity fluctuation of 10 only resulted in a significant variation in MIH and CHH gene expression when compared to the control(P < 0.05). According to our findings, L. vannamei may be highly capable of tolerating salinity fluctuation. When ambient salinity fluctuated at approx. 4, the increased MF and energy stores in organisms may aid to promoting shrimp growth. To determine the response of Litopenaeus vannamei to periodical salinity fluctuation, a 30-day experiment was conducted in laboratory. In this experiment, two salinity fluctuation amplitudes of 4 (group S4) and 10 (group S10) were designed. The constant salinity of 30 Levels of shrimp growth, molting frequency (MF), cellular energy status (ATP, ADP and AMP), as well as the expression of genes encoding molt-inhibiting hormone (MIH), crustacean hyperglycemic The results showed that periodical salinity fluctuation significantly influenced all indicators except MF which ranged from 13.3% in group S10 to15 .4% in group S4. In comparisonCompare shrimps cultured at the constant salinity of 30, those in group S4 showed a significant elevation in growth rate, food conversion efficiency, cellular energy status, ERP and MIH gene transcript abundance, However, the salinity fluctuation of 10 only resulted in a significant variation in MIH and CHH gene expression when compared to the control (P <0.05). According to our findings, L. vannamei may be highly capable of tolerating salinity fluctuation. When ambient salinity fluctuated at approx. 4, the increased MF and energy stores in organisms may aid to promote shrimp growth.