Chromium contaminated drug capsules drew much of world’s attentions. Although trace amount of chromium allowed to existence in the drug capsules, but the combined effects of chromium with other drug chemicals remain unclear. Therefore, the combined genotoxicity of hexavalent chromium [Cr (VI)] with nitroso drug chloroethylnitrosourea (ACNU) was examined using the Salmonella mutagenicity assay. The results showed that Cr (VI) and ACNU produced a dose-dependent increase in the revertants in TA 98 and TA 100 strains. In the individual chemical mutation assay, the positive mutagenicity response for Cr (VI) doses was above 2 mg per plate, and for ACNU above 5 mg per plate. In binary chemical mutation assay, the straightforward positive results could even be detected when the dose of Cr (VI) and ACNU both down to 1 mg per plate. It was indicated that neither Cr (VI) nor ACNU individually caused more genotoxicity to bacterial DNA at low levels. However, the two, working together, had significant revertant mutation effects. This means the combined genotoxicity effects of Cr (VI) and ACNU are more harmful than the individual exposure.