〔Abstract〕 To determine the expression of melanoma-associated antigens D4 (MAGED4) and SIRT7 in human glioma, and to analyze the potential effects of MAGED4 and SIRT7 on glioma cell proliferation. Method The MAGED4 and SIRT7 expression levels and their correlation were compared by the China glioma genome atlas (CGGA), Human Protein Atlas (HPA), and UALCAN databases. Survival analysis, ROC curve analysis, and Cox regression analysis were used to predict the outcome of MAGED4 and SIRT 7 in glioma patients. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis were used to explore the biological functions of MAGED4 and SIRT7 in glioma. Western blot experiment was used to investigate whether MAGED4 protein exerted its regulatory effects on the activity of the PI3K / AKT signaling pathway via SIRT7. The effect of MAGED4 on cell proliferation in glioma through SIRT7 was explored by CCK-8. Result The analysis results of CGGA, UALCAN, and HPA databases showed that the expression levels of MAGED4 and SIRT7 in glioma tissues were higher than those in normal brain tissue, and the expression were positively correlated. Results of survival, ROC, and Cox analysis showed that high expression of MAGED4 and SIRT7 mRNA were risk factors for poor prognosis in glioma. Results of KEGG enrichment analysis showed that MAGED4 and SIRT7 were associated with the PI3K/AKT signaling in glioma, and Western blot results showed that MAGED4 activated the PI3K/AKT signaling pathway by regulating SIRT7. The CCK-8 results showed that MAGED4 affected the proliferation of glioma cells through SIRT7. Conclusion MAGED4 and SIRT7 are highly expressed in glioma and associated with poor prognosis, and MAGED4 promotes glioma cell proliferation through activation of the PI3K/AKT signaling pathway by SIRT7.