The alternative disinfectant chloramine can lower the formation of carbonaceous DBPs (C-DBPs) but promote the formation of nitrogenous DBPs (N-DBPs), which are more cytotoxic and genotoxic. In this study, the combination of thermally activated persulfate pre-oxidation and post-chloramination (TA/PS-NH2Cl) was proposed to control the formation and reduce the toxicity of both C-DBPs and N-DBPs. The formation, speciation and toxicity of trihalomethanes, haloacetic acids, haloaldehydes, haloacetonitriles, halonitromethanes and haloacetamides, collectively defined as CX3R-type DBPs, under TA/PS-NH2Cl process were compared with processes of chlorination alone (Cl2), chloramination alone (NH2Cl) and coupled thermally activated persulfate pre-oxidation with post-chlorination (TA/PS-Cl2). Results showed that chloramination could reduce formation of C-DBPs and total organic halogen (TOX) while increase N-DBP formation, and the introduction of TA/PS pretreatment process slightly increased the formation of C-DBPs and TOX but sharply reduced the formation of N-DBPs with higher toxicity as well as brominated CX3R-type DBPs that are more toxic than their chlorinated analogues. By comprehensive toxicity calculation, an outright decline of both cytotoxicity and genotoxicity risk of CX3R-type DBPs was observed during TA/PS-NH2Cl process compared with Cl2, NH2Cl, and TA/PS-Cl2 processes. In summary, TA/PS-NH2Cl process was a potential effective method for integrally controlling the formation of CX3R-type DBPs and their toxicity and is suggested to be used to treat raw waters containing no bromide or low levels of bromide considering bromate caused by TA/PS pre-oxidation. The study may provide a feasible and economical method for DBP control on the background of global warming.