The wide applications of titanium dioxide nanoparticles (TNP) and ubiquitous cadmium (Cd) pollution increase the chances of their co-existence in the environment and also pose potential health risks to humans. However, toxicological understanding of effects of co-exposures of TNP and Cd to mammals is still lacking. In this study, non-lethal doses of TNP and CdCl₂ were intravenously co-administered to healthy or Concanavalin A (ConA)-induced acute hepatitis mice. Co-exposures of TNP and CdCl₂ increased the accumulation of Cd²⁺ in the liver of hepatitis mice, which was 1.42-fold higher than that of healthy mice. Co-exposures also caused liver damage only in hepatitis mice on the basis of histopathological and biochemical evidence. Further study showed that co-exposure upregulated hepatic oxidative stress, which further induced autophagy and apoptosis only in the liver of hepatitis mice. This finding underlines the potential toxicological consequences of co-exposures of TNP and CdCl₂ in hepatitis sufferers.