Abstract: With the improvement of aquaculture scale, the disadvantages of traditional aquaculture mode are constantly emerging, including waste and pollution of water sources. On this basis, the recirculating aquaculture system with aeration plug-flow device in pond is an exploration of efficient and energy-saving aquaculture mode, which has been developed rapidly at home and abroad. Water environment, as the place where fish live, is crucial to the growth of fish. A large number of studies have shown that dissolved oxygen, ammonia nitrogen and nitrite are the three important factors that affect the growth of fish. There are synergistic effects among dissolved oxygen, ammonia nitrogen and nitrite. Insufficient dissolved oxygen and high mass concentrations of non-ionic ammonia and nitrite can cause metabolic dysfunction of fish body and decrease of immunity, leading to the occurrence of fish diseases. Therefore, in order to explore the response of fish growth to water environment, and predict the growth rate of fish under the synergistic effect of water environment factors, the experiment was conducted on indoor recirculating aquaculture tilapia test with aerated plug-flow device with a continuous duration of 8 weeks. By changing the aeration flow, three conditions were set up in the experiment to observe the growth of tilapia during the breeding period, and the mass of the fish and water quality parameters such as dissolved oxygen, non-ionic ammonia and nitrite were regularly measured. The results showed that within a certain range, with the increase of dissolved oxygen mass concentration, the food conversion efficiency and specific growth rate of fish increased; with the increase of non-ionic ammonia mass concentration, the food conversion efficiency and specific growth rate of fish decreased. However, due to the small change in nitrite mass concentration and the safe mass concentration range, there was no significant effect on the food conversion efficiency and specific growth rate of fish in this experiment. Based on the results of the experiment, the specific growth rate of tilapia was nonlinearly fitted, and the growth prediction equation of fish was established, with R2 of 0.82. The validity and universality of the equation were verified by the measured data. The growth prediction equation showed that the increase of the initial mass of fish, stocking density, non-ionic ammonia and nitrite concentration could slow down the growth rate of the fish; while increasing the dissolved oxygen concentration could increase the growth rate of the fish. In the current situation of increasingly tight land, intensive farming is often adopted to improve the level of farming. With the increase of aquaculture density, the concentration of non-ionic ammonia and nitrite in the water environment increases, which have a negative impact on the growth rate of fish. It could improve the water environment and promote the healthy growth of fish by increasing dissolved oxygen. Although this prediction model is obtained under the aeration push flow cycle cultivation mode, it is also applicable to the other aquaculture water modes, making the response of fish growth to measurable water environmental factors, which provides convenience and reference for promoting the healthy development of aquaculture fish, the optimization of aquaculture system and the improvement of aquaculture benefits.