We investigated the expression and clinical significance of Rap1A in colorectal carcinoma (CRC) progression and its association with FGF2 signaling. We measured Rap1A levels in 44 CRC tissues and adjacent non-tumoral tissues and analyzed clinical indicators in recruited patients. Knockdown of Rap1A in HCT-8 and SW480 cells was performed, followed by functional experiments to assess proliferative, migratory, and invasive abilities. The regulatory effects of Rap1A on FGF2 signaling by measuring protein levels of FGF2, ERK, and JNK. The binding interaction between Rap1A and FGF2 was explored using a dual-luciferase reporter assay. Rap1A, a protein highly expressed in CRC tissues, has been implicated in CRC progression and metastasis. Through various experiments, we demonstrated the involvement of FGF2 signaling in Rap1A-mediated CRC progression. Knockdown of Rap1A resulted in decreased proliferation, migration, and invasion of CRC cells, accompanied by downregulation of FGF2, ERK, and JNK proteins. FGF2, identified as a target IP 2038 10920 On: T e, 05 Sep 2023 0623:48 gene of Rap1A, was found to be upregulated in CRC tissues. Overexpression of FGF2 counteracted the inhibitory effects Copyright: American Scientific Pub ishers of Rap1A knockdown on CRC cell abilities. In a mousmodel, Rap1A knockdown inhibited CRC growth, which was Delivered by Ingenta rescued by FGF2 overexpression. In summary, Rap1A is highly expressed in CRC, predicts metastasis, and promotes CRC cell abilities through activation of FGF2 signaling.