Mediator kinase Cyclin Dependent Kinase 8 (CDK8), a ubiquitously expressed transcriptional member of the CDK family, plays a pivotal role in transcriptional regulation and colorectal cancer (CRC) tumorigenesis. CDK8 is located at a region of recurrent copy number gain in a substantial fraction of CRC cases and regulates β-catenin activity as an oncogene. CDK19, a paralog of CDK8, shares nearly identical cyclin binding and kinase domains but diverges at the C-terminal tail, exists in a mutually exclusive manner in Mediator. As hyperactivation of Wnt/β-catenin signaling is a hallmark of CRC, it highlights the potential of CDK8/19 as therapeutic targets in CRC treatments. While some studies showed CDK8/19 knockdown have tumor suppressive capabilities, there were also researches reporting toxicity of the CDK8/19 inhibitors. Therefore, there is a critical need to understand the role of CDK8/19 in regulating intestinal homeostasis and how they contribute to intestinal tumorigenesis. In order to understand the mechanisms, we utilized a series of genetically engineered mouse models as well as derived organoid models. Our study showed CDK8/19 knockout is dispensable for the adult intestine. We identified CDK8/19 as critical regulators of intestinal secretory lineage differentiation through regulating Atoh1 related enhancers. However, CDK8/19 knockout in a mouse model with Apc deletion showed accelerated tumorigenesis with mechanisms need to be further characterized. Together, these results identified CDK8/19 as novel regulators in intestinal secretory lineage differentiation. However, further studies are needed to understand the oncogenic or tumor-suppressive roles of CDK8/19 in different stages of CRC before clinical application.