In our study, TCF19 was found to be upregulated in microsatellite instability (MSI) endometrial cancer and was associated with poor prognosis and immune exhaustion signature. Elevated TCF19 enhanced cell proliferation and migration, which promoted tumorigenicity under non-immunological background; Moreover, tumoral TCF19 expression could also promote CD8+T cell exhaustion in tumor immune microenvironment, which facilitated immune escape and tumor development. Therefore, TCF19 could be a promising biomarker and effective therapeutic target for MSI endometrial cancer. Overall design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) was performed in TCF19 over-expression and control Ishikawa cells using anti-TCF19 antibody.