Regorafenib (RG) was an oral multi-kinase inhibitor with poor water solubility. In order to enhance the drug's solubility, dissolution and bioavailability, the binary molecular chaperone drug between RG and β-cyclodetrin (β-CD) had prepared by co-crystallization. The structure of RG-β-CD was characterized by thermal analysis, powder X-ray diffraction, infrared spectroscopy and nuclear magnetic resonance. Phase-solubility study revealed the higher solubility and complexing ability of β-CDwith RG.The solubility and dissolution of RG-β-CD was significantly enhanced in pH 1.2 medium, pH 6.8 PBS buffer solution and distilled water compared to RG. In vivo distribution and antitumor studies revealed that the bioavailability of RG-β-CD was increased when β-CD mated with RG. Therefore, these findings could provide a suitable pharmaceutical dosage to enhanced therapeutic activity.