Microarray-based transcriptomics and one-dimensional proton nuclear magnetic resonance ((1)H NMR) based metabonomics approaches were employed to investigate the health effects of nitrogenous disinfection byproducts (N-DBPs) of trichloroacetamide (TCAcAm) on mice. Mice were exposed to TCAcAm at concentrations of 50, 500, and 5000 μg/L for 90 days, and hepatic transcriptome and serum metabonome and histopathological parameters were detected in comparison with those of control. TCAcAm esposures resulted in liver inflammation, weight loss (in 5000 ug/L TCAcAm group), and alterations in hepatic transcriptome and serum metabonome. Based on the differentially expressed genes and altered metabolites, several significant pathways were identified, which are associated with lipid, xenobiotics, amino acid and energy metabolism, and cell process. Moreover, integrative pathway analyses revealed that TCAcAm exposure in this study induced hepatotoxicity and cytotoxicity. These results also highlight the noninvasive prospect of transcriptomic and metabonomic approaches in evaluating the health risk of emerging N-DBPs.