BACKGROUND: Thousand and One Kinase 1 (TAOK1), a member of the MAPK kinase family, plays a crucial role in processes like microtubule dynamics, DNA damage response, and neurodevelopment. While TAOK1 is linked to tumorigenesis, its oncogenic role across cancers remains unclear. This study aims to explore the relationship between TAOK1 expression, prognosis, and immune function in various cancers. METHODS: We analyzed TAOK1 expression in multiple cancers using TCGA, GEO, CCLE, and other bioinformatics databases. The correlation between TAOK1 expression and immune cell infiltration was assessed with the ESTIMATE algorithm. We also examined associations with tumor stemness, DNA methylation, gene copy number alterations, and drug sensitivity. The oncogenic role of TAOK1 was further evaluated in vitro with SiHa and A2780 cells and in vivo with TAOK1 overexpression in SiHa cells. RESULTS: TAOK1 is a key prognostic biomarker in various cancers and its high expression is associated with poor prognosis. It showed a significant negative correlation with immune cell infiltration and immune checkpoints. GSEA identified its involvement in key tumour pathways, highlighting the therapeutic potential of inhibiting the TAOK1 gene. The high expression of TAOK1 is associated with DNA methylation and gene copy number variation, and in addition its upstream regulator, EP300, is closely associated with TAOK1 expression. In vitro cellular experiments demonstrated that inhibition of TAOK1 reduced the proliferation of SiHa and A2780 cells, whereas overexpression of TAOK1 in SiHa cells promoted growth. These findings were further validated in vivo by nude mouse tumourigenicity assay and human tissue immunohistochemistry. CONCLUSION: TAOK1 serves as a promising prognostic biomarker and potential therapeutic target, especially for cervical cancer. These results support its clinical potential in cancer prognosis and treatment strategies.