【Abstract】 Objective To study the effect of VB12, Folic acid combined with tetralogy on HP associated chronic atrophic gastritis(HPCAG) and its effect on ECad, MMP9, Cyclin E. Methods A total of 186 cases of HP～CAG patients treated in our hospital from January 2013 to December 2017 were included into this study, and divided into experimental group (n=93) and control group (n=93), using the random number table method. Patients in control group were performed quadricombination therapy, and those in experimental group were treated by quadricombination therapy, VB12 and Folic acid. Before and after treatment, the scores of gastric mucosal microscopic examination and gastric mucosal pathological examination, inflammatory factors such as tumor necrosis factorα(TNFα), interleukin1 (IL1), interleukin8 (IL8) and highsensitivity Creactive protein (hsCRP), Tumor factors such as ECad, matrix metalloproteinase9 (MMP9), Cyclin E, adverse reactions and other indicators of the two groups were observed. Results After treatment, the scores of gastric mucosal microscopic,pathological examinations and TNFα, IL1, IL8, hsCRP, MMP9, Cyclin E of the two groups were lower than before treatment, ECad of the two groups were higher than before treatment (P＜005), the scores of gastric mucosal microscopic and pathological examinations TNFα, IL1, IL8, hsCRP, MMP9, Cyclin E in experimental group were lower than those in control group, ECad was higher than that in control group (P＜005). The effective rate of experimental group (9677%) was higher than that of control group (7742%) (P＜005). The HP clearance rate of experimental group(9677%) was higher than that of control group (7957%) (P＜005). During the treatment, no obvious adverse reaction was found in the two groups. Conclusion VB12 and Folic acid combined with tetralogy therapy in the treatment of chronic atrophic gastritis can effectively inhibit the expression of MMP9, Cyclin E, promote the expression of ECad and inhibit the malignant progression of HPCAG.