Potassium monopersulfate (KMPS), tetrakis hydroxymethyl phosphonium sulfate (THPS), bacillus subtilis (BS) and chitosan (CS) are four new types of water quality regulators, which play an important role in aquaculture. In the 35-day Oreochromis niloticus (GIFT tilapia) feeding trial, all four drugs could slow down the increasing rate of ammonia nitrogen, nitrite, active phosphate and harmful substances of water in the process of GIFT tilapia culture. At the same time, the growth performance, organ index, blood physiology and biochemistry were improved, acid phosphatase (ACP), alkaline phosphatase (AKP), superoxide dismutase activity (SOD) and total antioxidant capacity(T-AOC) of serum were increased, and feed coefficient (CF) was reduced. In KMPS and THPS groups, the contents of glutamic oxaloacetic transaminase (AST), glutamic pyruvic transaminase (ALT) and creatinine (Cr) of serum were significantly increased, and the hepato-somatic index (HSI) was significantly decreased during the whole feeding process. In KMPS and THPS groups, the histomorphology of liver showed obvious pathological changes. The results showed that KMPS, THPS, BS and CS could effectively improve the water quality, growth performance and immune function of GIFT tilapia. Nevertheless, frequent use of KMPS and THPS will adversely affects organ and tissue of GIFT tilapia.