Curcumin-loaded poly (α-isobutyl cyanoacrylate) microspheres (Cur-HP-β-CD-PiBCA) were prepared by one-step emulsification with α-isobutyl cyanoacrylate as materials, poloxamer 188 as emulsifier, and curcumin complex with hydroxypropyl-β-cyclodextrin (Cur-HP-β-CD) as drug prepared by kneading method. Effects of emulsifier and drug concentration on microspheres size and distribution, drug loading and encapsulation efficiency were investigated in detail. And the curcumin release of drug-loaded microspheres was also studied. Results showed that as the emulsifier concentration increased from 0.01% to 0.07%, particle size of the drug-loaded microspheres decreased while particle size distribution, drug loading and entrapment efficiency increased. The optimized concentration of surfactant was 0.05%. With increasing the concentration of drug from 0.03% to 0.07%, drug loading of Cur-HP-β-CD-PiBCA increased, but encapsulation efficiency decreased. Additionally, the results of drug release experiments revealed that the higher drug loading of Cur-HP-β-CD-PiBCA was, the lower cumulative release percentage was. Drug-loading of cumulative inclusions in HP-β-CD by PiBCA can improve its wettability, and increase the degree of dissolution and bioavailability.