Collectively, our findings establish a novel role of regorafenib as an agonist of SHP-1 tyrosine phosphatase activity by direct disruption of the association between N-SH2 and catalytic PTP domain of SHP-1 and then downregulating the expressions of p-STAT3Tyr705 and its related survival factors such as Cyclin D1 and Mcl-1, thereby, triggering apoptotic induction in CRC (Figure 6). Here, MCL1 is linked to colorectal carcinoma.