Objective RAD23B, a DNA repair-related protein, has been implicated in the progression of various malignancies. This study aimed to investigate the role of RAD23B in promoting colorectal cancer (CRC) metastasis and to elucidate the underlying molecular mechanisms.Methods RAD23B was overexpressed in CRC cell lines SW480 and HCT-8, with empty vectors serving as controls.Cell proliferation, migration, and invasion were assessed using Cell Counting Kit-8 (CCK-8) and Transwell assays.A xenograft mouse model was used to evaluate metastatic potential in vivo.Transcriptomic analysis by RNA sequencing (RNA-seq) was performed to identify signaling pathways regulated by RAD23B.Western blotting was used to analyze the expression of RAD23B, Talin1, Integrins αv/β1, phosphoinositide 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (AKT), phosphorylated AKT (p-AKT), and matrix metalloproteinase 9 (MMP9).Results RAD23B overexpression significantly enhanced CRC cell proliferation, migration, and invasion both in vitro and in vivo.RNA-seq revealed that RAD23B upregulated Talin1 and Integrins αv/β1, leading to activation of the PI3K/AKT signaling pathway. Moreover, RAD23B promoted MMP9 expression, contributing to enhanced invasive potential.Conclusion RAD23B promotes colorectal cancer liver metastasis through activation of the Talin1/Integrin/PI3K/AKT/MMP9 axis.