Clusterin () is a chaperone-like protein that has been demonstrated to have a direct relationship with cancer occurrence, progression, or metastasis. Clusterin was downregulated in tumor tissues using three datasets of tongue squamous carcinoma from the Gene Expression Omnibus. We further retrieved datasets from The Cancer Genome Atlas and Gene Expression Omnibus to thoroughly investigate the carcinogenic consequences of Clusterin. Our findings revealed that decreased Clusterin expression in malignancies was associated with a worse overall survival prognosis in individuals with multiple tumors; Clusterin gene deep deletions were found in almost all malignancies and were connected to most cancer patient's prognosis, Clusterin DNA methylation level was dependent on tumor type, Clusterin expression was also linked to the invasion of cancer-associated CD8+ T-cells and fibroblasts in numerous cancer forms. Moreover, pathway enrichment analysis revealed that Clusterin primarily regulates biological processes such as cholesterol metabolism, phospholipid binding, and protein-lipid complex formation. Overall, our pan-cancer research suggests that Clusterin expression levels are linked to tumor carcinogenesis and prognosis, which contributes to understanding the probable mechanism of Clusterin in tumorigenesis as well as its clinical prognostic significance.