The Box–Behnken experimental design and response surface methodology were employed to optimize the preparation of the aspirin micro-porous osmotic pump tablets. The core of the tablet is prepared with aspirin and β-CD inclusion, then osmotic pump tablets were obtained by coating a layer of cellulose acetate containing PEG 4000 as porogenic agent. The in vitro release test showed that the aspirin inclusion complex microporous osmotic pump tablets prepared by this process had a cumulative release rate of 1.5% and 1.6% within 0-2 hours in artificial gastric juice compared to commercially available aspirin enteric coated tablets; after adjusting the release medium to pH 6.8, there was no significant difference in the cumulative drug release between the two formulations at 10 hours. And the inclusion complex microporous osmotic pump tablet showed zero order release and complete release within 12 hours (cumulative release rate> 90%), indicating the possibility of reducing drug damage to the gastric mucosa.