This study aimed to compare the toxicity reduction performance of conventional drinking water treatment (CT) and a treatment (NT) with quaternized magnetic microspheres (NDMP) based on chemical analyses. Fluorescence excitation-emission-matrix combined with parallel factor analysis identified four components in source water of different rivers or lake, and the abundance of each component differed greatly among the different samples. Compared with the CT, the NT evidently reduced the concentrations of dissolved organic carbon, adsorbable organic halogens (AOX), bromide and disinfection by-products. Toxicological evaluation indicated that the NT completely eliminated the cytotoxicity, and greatly reduced the genotoxicity and oxidative stress of all raw water. In contrast, the CT increased the cytotoxicity of Taihu Lake and the Zhongshan River water, genotoxicity of Taihu Lake and the Mangshe River water, as well as the levels of superoxide dismutase and malondialdehyde of the Mangshe River water. Correlation analysis indicated that the AOX of the treated samples was significantly correlated with the genotoxicity and glutathione concentration, but exhibited no correlation with either of them for all the samples. As it can effectively reduce pollutant levels and the toxicities of drinking water, NDMP might be widely used for drinking water treatment in future.