Adaptive responses to diverse microbial pathogens might be limited in relatively few types. Host cell responses to pathogens are believed to be patterned or stereotyped along with species or class. We tried to compose the host response to Mycoplasma in terms of cellular gene expression. Although gene expression profile of two host HeLa and 293 cells were quite different each other, 30 genes were differentially expressed by mycoplasma infection in both of HeLa and 293 cells. Six of them (PR48, MADH4, MKPX, CRK, RBM7, NEK3) were related to cell cycle or proliferation. Another category of genes like IL1 HY1, KLRF1, TNFSF14, GBP1 were host defense to elicit immune responses. With this set of genes, we establish the prediction model for mycoplasma contamination.