Periphyton are widely found in natural water bodies. They have strong vitality and can reproduce and migrate by releasing spores/gametes. Conventional growth models of periphyton usually only involves the algal growth process and the influence of hydrodynamics, lacking the consideration of the reproduction and migration process, which is also an integral part of the life cycle of periphyton. In this paper, a growth-migration model suitable for periphyton was constructed by introducing the reproduction and migration process into the conventional growth model, which was then calibrated and verified using relevant experimental results. According to the qualitative research of algal proliferation issues in the middle route of the South-to-North Water Transfer Project, periphyton could proliferate abnormally when the discharge velocity was lower than 0.4 m/s and thus gathered at the cannel corners or side walls. Increasing the water discharge of the main canal could effectively increase the average flow velocity and reduce the growth of periphyton. The average density of the periphyton in the main canal when the flow velocity was 350 m3/s only accounted for 20% of that when the flow velocity was 180 m3/s. The simulation results are consistent with the actual situation, and this research can provide some reference for the further treatment of periphyton proliferation in the middle route of the South-to-North Water Transfer Project.