Background: G6PC has emerged as a prognostic biomarker and potential therapeutic target in cancer, but its role in renal cell carcinoma (RCC) remains unclear. Methods: We analyzed G6PC expression using TCGA, GEO, and clinical data, with protein validation via HPA. Pathway enrichment, immune infiltration, and methylation analyses were performed. Prognostic value was assessed by Cox regression and Kaplan–Meier analysis. In vitro and in vivo experiments evaluated the effects of G6PC dysregulation.