Inclusion complexes of genistein with β-cyclodextrin were prepared. An orthogonal test with three factors including molar ratio of β-CD versus genistein, inclusion temperature and stirring time was designed to investigate the optimum technology for the inclusion reaction of genistein with β-Cyclodextrin (β-CD). The complex was characterized with UV and IR absorption spectrometry, thermogravimetry (TG) analysis, derivative thermogravimetry (DTG) and differential scanning calorimetry (DSC) in comparison with the corresponding hosts and guests. The present study also examined the stability of the complex that was stored at special temperature by monitoring the change of genistein with time. The results obtained in this paper indicate that both β-Cyclodextrin and the host genistein molecule formed molar ratio of 1:1 complex. Its thermal stability and water-solubility are improved significantly and the information can serve as an important basic data for further processing in further application fields.