In present work, the genotoxicity of Hg2+, Ag+, Cr6+, Ni2+, Pb2+, Co2+, Mn2+, Zn2+, and Cr3+ was investigated via a quantitative toxicogenomics assay, to understand the toxic mechanism of heavy metals with greater depth. Under the experimental conditions, Hg2+, Ag+, and Cr6+ showed a more serious toxic impact on the expression of functional genes (eg., oxyR, katG, grxA, osmE, emrE, dinG) than Ni2+, Pb2+, Co2+, Mn2+, Zn2+, and Cr3+, while the protein, oxidative, and membrane stress response pathways were more sensitive to the toxicity of Hg2+, Ag+, and Cr6+ than the DNA and general stress response pathways. Compared with the other kinds of heavy metals, Ni2+, Pb2+, Co2+, and Mn2+ altered the expression of functional genes (uvrY, recX, mutY, and sbmC) related to the DNA stress response pathways more seriously, while Zn2+ and Cr3+ changed the expression of the functional genes (yfjG, ydgL, ssrA, and osmC) associated with the general stress response pathway more significantly. Meanwhile, the toxicity of Ni2+, Pb2+, Co2+, and Mn2+ was slightly higher than that of Zn2+ and Cr3+ in terms of the total value of transcriptional effect level Index (TELI) by detecting the promoter activities of different functional genes. In addition, to survive the toxicity of heavy metals, the expression of multidrug efflux genes (ydgL, cyoA, emrA, and emrE) and toxicity-resistant genes (Ion, dnaJ, clpB, mutY, dnaK, rpoD, sbmC) mainly functioned.