Aiming at the challenge of how oral drug delivery systems protect drug molecules from environmental influences in human body, a pH value-sensitive sodium alginate-montmorillonite composite microsphere (MMT/SA) was synthesized by an emulsification gel method, which was used to load anticancer drug doxorubicin hydrochloride (DOX), and overcome the biochemical barrier of gastrointestinal tract while protecting drug molecules. The effect of raw material (MMT pretreatment and content) on the morphology of microspheres was investigated, and the size of microspheres with a uniform distribution was controlled to be 20 μm. The drug loading rate of DOX/MMT/SA is 14.7%, indicating different drug release effects in simulated gastric juice and artificial intestinal juice. The cumulative release rate of DOX/MMT/SA in simulated gastric juice (i.e., 31.7%) is greater than that in artificial gastric juice (i.e., 15.8%), and it has a killing effect on the cancer cells.