Two acute toxicity tests (luminescent bacteria assay and cladoceran assay) and one genotoxicity test (broad bean assay) were used to evaluate whole effluent toxicity during the standard anion exchange resin-based pilot-scale sewage tertiary treatment that stably achieved significant dissolved organic carbon and inorganic ions reduction. The effect of six representative inorganic ions (i.e., Cl−, SO42−, NO3−-N, NO2−-N, NH4+-N and PO43−-P) on the acute toxicity and genotoxicity was further investigated. Significant whole effluent genotoxicity reduction was observed as an ∼57% micronucleated cell frequency reduction and ∼46% mitotic index increment during the pilot-scale periods, which should be attributed to significant organic removal since no significant (p≥0.116) increase in genotoxicity was observed with the increase in these ionic concentrations. However, no significant (p≥0.14) reductions were observed for whole effluent acute toxicity using two acute toxicity assays during the pilot-scale periods, and these inorganic ions, especially NH4+-N, contributed considerably to the acute toxicity. Based on Pearson correlation coefficients, whole effluent acute toxicity showed significant positive (p<0.001, r≥0.758) correlations with the NH4+-N concentration. Two optimal models were finally developed using step-wise multiple linear regression to predict the whole effluent acute toxicity via NH4+-N concentrations.