〔Abstract〕 To investigate the expression of TIPE3 in colorectal cancer (CRC) and its correlation with tumor immune infiltration and prognosis . Methods The expression of TIPE3 in tumor and adjacent normal tissues from 110 CRC patients was detected using real-time fluorescence quantitative enzyme chain reaction ( qPCR) , Western blot (Western blot ) , immunohistochemistry (IHC) , bioinformatics analysis , and single-cell RNA sequen-cing (scRNAseq) . The association between TIPE3 expression and clinicopathological factors , prognosis , and im- mune cell infiltration was analyzed . Results Transcriptomic and proteomic analyses revealed that among the TIPE family , TIPE (P < 0. 05) and TIPE3 (P < 0. 001) were significantly upregulated in CRC tissues compared to adja- cent normal tissues , with TIPE3 showing the most pronounced increase . IHC further confirmed that TIPE3 expres- sion was significantly higher in CRC tissues ( P < 0. 001) . Kaplan-Meier survival analysis indicated that high TIPE3 expression was associated with reduced survival and poorer prognosis . Immune infiltration analysis demon- strated that patients with high TIPE3 expression exhibited fewer CD8 + T cells and CD20 + B cells but more CD66b + neutrophils , suggesting a correlation between TIPE3 and unfavorable tumor prognosis . Additionally , scRNA-seq of CRC tissues yielded results consistent with the IHC findings . Conclusion TIPE3 expression in CRC is associated with tumor immune infiltration , and its upregulation predicts poor prognosis , indicating its potential as a therapeutic and preventive target in CRC .