In 2006 and 2007, five sampling stations were set up in Xieshui River and its tributaries to study the macro-invertebrate communities, and measure physicochemical parameters and contents of different forms of arsenic. A comparative analysis and multivariate statistical methods were used to explore the effects of arsenic pollution on the macro-invertebrate communities. In this study, sixty species were identified, including 39 aquatic insects, 10 mollusks, 5 oligochaetes, 1 crustacean, and 5 others. Results of the comparative analysis indicated that the macro-invertebrate communities at the station with serious arsenic pollution tended to be simple and showed a significant decreasing in density, biomass, and biodiversity in comparison with the other stations. Arsenic pollution also had a major effect on the dominant species and groups. For instance, EPT taxa disappeared at the station with serious arsenic pollution, and chironomids that belong to the genus were very tolerant to high concentrations of arsenic. Results of the functional feeding groups (FFGs) analysis indicated that the predators were more tolerant to arsenic pollution, while the scrapers, filterers, and collectors were relatively sensitive to arsenic pollution. Results of a non-metric multidimensional scaling (nMDS) analysis showed that when the concentration of inorganic arsenic decreased to the range between the criteria continuous concentration (CCC) and the criteria maximum concentration (CMC), the effects of inorganic arsenic on the macro-invertebrate communities seemed to be insignificant. Results of a BVSTEP (Bio-Env Step-Wise Procedure) analysis showed that water temperature, rotifer density, trivalent arsenic, pentavalent arsenic, and total inorganic arsenic greatly influenced species appearance, while rotifer density and various forms of arsenic had a considerable impact on the species composition.