Objective: To investigate the protective effect of sulforaphane (SFN) against titanium dioxide nanoparticles (TiO₂ Nps)-induced liver injury in mice. Methods: Fifty 6-week-old male C57BL/6J mice were randomly divided into a control group (NC)， a TiO₂ Nps model group (100 mg/kg)， a TiO₂ Nps+low-dose SFN administration group (0.5 mg/kg)， a TiO₂ Nps+medium-dose SFN administration group (1 mg/kg)， a TiO₂ Nps+high-dose SFN administration group (2 mg/kg)， and 10 in each group. Blood was collected from the orbits after 9 weeks， and the livers of the mice were retained. The serum levels of ALT and AST， oxidative stress and inflammation were detected in the liver tissues of mice. HE staining was used to observe the histopathological and morphological changes in the liver tissues of mice， and immunohistochemistry staining was used to detect the expression of F4/80 proteins in the livers of mice. Protein immunoblotting was used to detect the expression levels of OGG1， NF-κb， ERK and p-ERK proteins. Results: Compared with the control group， the serum levels of AST and ALT were significantly increased in the model group (P<0.01)； compared with the model group， each SFN administration group significantly reduced the serum levels of ALT， AST and TBIL (P<0.01)； significantly increased the GSH/GSSG ratio of the liver tissues as well as the level of SOD (P<0.01)； and significantly reduced the level of MDA in the liver tissues of the mice (P<0.05， P<0.01). Real-time quantitative PCR results showed that compared with the model group， the mRNA levels of IL-6 and TNF-α were significantly reduced in the SFN medium- and high-dose administration group (P<0.05， P<0.01). Western blotting results showed that compared with the model group， the protein expression levels of NF-κb， p-ERK and ERK were significantly down-regulated in the administration group (P<0.05， P<0.01). HE staining results showed that compared with the model group， the administration group had HE staining results showed that the vacuolization degree of hepatocytes in the administered group was improved compared with that in the model group. Immunohistochemical staining showed that F4/80 expression was reduced in the administered group compared with the model group. Conclusion: SFN was able to attenuate TiO₂ Nps-induced changes in liver injury， oxidative stress and inflammatory indexes in mice， suggesting that SFN could alleviate TiO₂ Nps-induced oxidative stress and inflammatory responses and might act through the NF-κb-ERK/p-ERK pathway.