Abstract: Objective to study the efficacy and mechanism of Renzhu Jianwei Granules in treating chronic atrophic gastritis (CAG) with the precancerous lesions of gastric cancer, CAG rat models were induced using N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) comprehensive factor modeling method. After successful modeling, Renzhu Jianwei Granules were administered by gavage. Evaluating the efficacy of Renzhu Jianwei Granules by observing their effects on gastric acid pH, food intake, body weight, serum levels of pepsinogen (PG), gastrin (GAS), motilin (MTL), and inflammatory factors TNF-α, IL-1α, and IL-6 in CAG rats; Hematoxylin-Eosin (H&E) staining and Alcian blue-periodic acid Schiff (AB-PAS) staining were used to observe pathological changes in the gastric antral tissue; TUNEL fluorescence staining was used to observe apoptosis of gastric mucosal epithelial cells; immunofluorescence staining was used to detect the expression of PCNA and p53 proteins in the gastric mucosa; qRT-PCR was used to detect the mRNA expression of p53, Mdm2, Bcl-2, Bax, and Tnf-α, Il-1α, Il-6 in gastric tissue; Western blot was used to detect the protein expression of PTEN, Akt, NF-κB, p53, MDM2, Bcl-2, Bax in gastric tissue, and immunofluorescence staining technology was used to detect the protein expression of Bcl-2/Bax in gastric tissue. Animal experiments approved by the Ethics Committee of China Pharmaceutical University (approval No. 2022-09-029). The results show Renzhu Jianwei Granules significantly reduced the gastric acid pH in rats, increased food intake and body weight, and decreased the serum levels of PGI/PGⅡ, GAS, MTL, TNF-α, IL-1α, IL-6 (P < 0.01); increased the mRNA expression levels of p53, Bax in the gastric antral tissue (P < 0.05, P < 0.01), and decreased the mRNA expression levels of Mdm2, Bcl-2, Tnf-α, Il-1α, Il-6 in the gastric tissue (P < 0.01); significantly increased the protein expression levels of PTEN, p53, Bax in the gastric tissue (P < 0.05, P < 0.01), and downregulated the expression of p-NF-κB, p-Akt, MDM2, Bcl-2 proteins (P < 0.05, P < 0.01). To sum up, Renzhu Jianwei Granules treat CAG by intervening in the PTEN/Akt/p53 pathway, inducing cell apoptosis, and preventing precancerous lesions.