Objective Establish the miＲNA expression profiling under environmental carcinogens and gene mutations，to provide some new clues for further study on the mechanism of tumorgenesis． Methods Under the same condition，mice were first prepared in SHP2 + / + normal ( wild type，Wt) and SHP2D61G/ + activating mutation ( gain-offunction mutation，GOF mutation) of immortalized fibroblast cells( mouse embryonic fibroblasts，MEFs) ，acute treat MEFs cells with 0. 5 μmol /L As2 O3 48 hours，then extract the cell total ＲNA． Use the analysis of miＲNA hybridization to establish the miＲNA( microＲNA，miＲNA，miＲ) expression profiling，screening the miＲNAs which differential expression significantly，then validated by ＲT-PCＲ． Ｒesults After treated the SHP2 + / + MEFs and SHP2D61G/ + MEFs with As2 O3，dozens of miＲNAs showed differential expression． The expression of miＲNAs increase or decrease in different SHP-2 + / + MEFs or SHP-2D61G/ + MEFs when treat with As2 O3 or not，at the same time，we discovered some miＲNAs show the same change along with the As2O3 treating and SHP2D61G/ + activating mutation，such as mmu-miＲNA-100 ( down regulation) and mmu-miＲNA-1907( up regulation) ． Conclusion Gene mutation and environmental pollution can effect the miＲNAs expression profiling of MEFs significantly， these change maybe the basis of cells malignant transformation and tumourgenesis．