Taipu River connects East Taihu Lake and Huangpu River. It is the main channel for flood discharge from East Taihu Lake to the downstream, and also the important water supply source for the upper reaches of Huangpu River. We set five fixed sampling sites along the Taipu River and carried out seasonal surveys from October 2017 to June 2018. Community structure of benthic macroinvertebrates and corresponding influential factors were analyzed based on these surveys. A total of 25 species of benthic macroinvertebrates were collected, belonging to 3 phyla, 6 classes, and 14 families. Among these assemblages, bivalves represented by Corbicula fluminea and gastropods represented by Bellamya aeruginosa were the dominant groups. The significant differences (P<0.05) were found in the abundance, biomass and diversity of benthic macroinvertebrates between the different sites, but not between the different seasons (P>0.05). Cluster and NMDS analysis showed that the difference between the sampling sites was more obvious than that between the sampling seasons to benthic macroinvertebrates. The species composition characteristics of the benthic macroinvertebrates in the Taipu River were closely related to the hydrological connectivity to the East Taihu Lake. The distribution characteristics of the benthic macroinvertebrates along the Taipu River were greatly affected by human disturbance and habitat conditions such as water nutrient level, substrate type and habitat heterogeneity, etc. The interaction mechanisms among them need further studies.