Proteolysis Targeting Chimeras (PROTACs) based on multi-target inhibitors have been reported several times recently. The advantages of PROTACs technology and the synergistic mechanism of multi-target drugs endow this class of protein degraders with special research significance. Herein, twelve new PROTACs based on Sunitinib and VHL-ligand were synthesized and evaluated for their in vitro anticancer activities. Among them, PROTACs 5 (IC<sub>50</sub> = 2.9 ± 1.5 μM) exhibited the most significant antiproliferative activity against HL-60 cells. Western blot results showed that PROTAC 5 reduced the protein levels of FLT-3 and c-KIT in HL-60 cells, and induced the degradation of FLT-3 via the ubiquitin-proteasome system. Moreover, PROTACs 5 and 6 reduced the protein levels of FLT-3 in K562 cells. These results suggest that PROTAC 5 has the potential for further research, especially in combination with small molecule kinase inhibitors to study multidrug resistance of tyrosine kinase inhibitors in cancer treatment.