Abstract: Objective To investigate the effects of doxorubicin on the proliferation and apoptosis of gastric cancer BGC823 cells under different pH conditions and the preliminary mechanism. Methods The effect of doxorubicin (ADM) cultured under different pH conditions on the proliferation of gastric cancer cell line BGC823 was detected by cell viability assay kit (CCK-8); Morphology of apoptotic cells were observed under fluorescence microscope; The apoptosis of BGC823 was assessed with Annexin V-PI; The expression of p-AKT, BCL-2 and NF-κB genes and proteins in gastric cancer cells were detected by qRT-PCR. Results ①The half-inhibitory concentration (IC₅₀) of ADM on gastric cancer BGC823 cells was 5.277 μg/mL. Considering the toxicity of chemotherapy drugs and subsequent experiments, the ADM dose was selected to be 1/4 times the IC₅₀ value of the cell line (1.319 μg/mL) for subsequent experiments; ②With the increase of pH, the inhibitory effect of ADM on the proliferation of BGC823 cells was enhanced. When the pH reached 7.4, the inhibition of proliferation was the most obvious. ③With the increase of pH, the apoptosis of BGC823 cells increased significantly with ADM. When the pH reached 7.4, the pro-apoptotic effect was the most obvious, and the pH concentration was further increased, and the ability to promote apoptosis was not obvious; ④Under different pH (pH 6.8-7.6) environment, the expression levels of BCL-2, NF-κB and p-AKT genes decreased significantly with the increase of pH after ADM treatment. Conclusion Increasing the extracellular pH can significantly increase the ability of ADM to inhibit cell proliferation and promote apoptosis in BGC823 cells. The anti-tumor effect of this pH-related ADM may be achieved by inhibiting the phosphorylation of AKT and preventing the expression of anti-apoptotic proteins such as NF-κB and Bcl-2.