Introduction Salt inducible kinases (SIKs) have a role in various biological process, including tumourigenesis in a tissue-dependent manner. However, their role in colorectal cancer (CRC) has yet to be established. We hypothesise that SIKs are differentially expressed in CRC, both promoting and preventing tumourigenesis. Methods SIK mRNA expression was determined within the Cardiff CRC cohort using reverse transcription-quantitative PCR and clinicopathological features were evaluated. Kaplan-Meier survival curves were created. SIK protein expression in CRC tissue were analysed using immunohistochemistry. SIK knockdown (KD) models were created to investigate the role of SIKs on barrier function and migration in vitro. Results Low SIK levels within CRC tissue were associated with poorer clinicopathological features. At the protein level, SIKs were downregulated in CRC tissue. Reduced expression of SIK2 and SIK3 were linked to poorly differentiated tumours. SIK KD induced different effects on cell barrier function, depending on the cell type. SIK KD increased cell migration in HT115 cells but reduced it in HRT18 cells. Conclusion Following translation, SIK expression was lower in CRC tumours than in normal tissue. Low SIK levels correlated to poorer clinicopathological characteristics, demonstrating their protective role in CRC. SIK loss contributed to cell-cell barrier dysregulation in vitro, revealing a possible mechanism of how SIKs regulate the metastatic potential of tumours. We demonstrate for the first time, the expression and role of all three SIKs in the tumourigenesis of CRC. This novel discovery has revealed possible therapeutic targets and biomarkers.