The study presented here investigates the effect of HMGB1 knockout on the sensitivity of mouse embryonic fibroblasts treated with the anticancer drug cisplatin. We evaluated both the growth inhibition by cisplatin and cisplatin-induced cell death in the Hmgb1(-/-) cells and its wild-type counterpart. No significant differences were observed in the responses of these cells to cisplatin, indicating that HMGB1 does not play a significant role in modulating the cellular responses to cisplatin in this context. Since HMGB1 significantly enhances the cytotoxicity of cisplatin in other cells, these results illustrate the importance of cell type in determining the ability of this and probably other cisplatin-DNA-binding proteins to influence the efficacy of the drug.