Oral liquid has the advantages of large drug loading, simple preparation and rapid effect. The substances of medicine and food homology (SMFH) are mostly developed into the form of oral liquid and prepared by high-temperature steam sterilization (HPSS). However, due to the complex composition of the solution, it is easy to be affected by HPSS and produce a series of unstable phenomena, which has become the key to hinder the development of the medicine and food homology oral liquid (MFHOL). Based on the characteristics of HPSS, this paper analyzed the chemical composition and physical phase interaction in the solution, discussed the mechanism and influencing factors of MFHOL instability induced by this method, as well as put forward feasible future solutions. Through the analysis and summary of the literature on oral liquid instability, it was found that HPSS can cause dramatic changes in the chemical composition of MFHOL, lead to changes of the physical phase, as well as produce a series of chain reactions, which seriously affect its stability. At the same time, this paper introduced the new sterilization technology that can be applied to the production of MFHOL in the future, put forward the personalized sterilization program and the establishment of intelligent continuous sterilization system according to the characteristics of SMFH. So as to provide the corresponding theoretical basis for the efficient and reasonable sterilization of MFHOL, in order to promote its further development.