High-pressure processing (HPP) entails the pasteurization of food using pressure in the 100–600 MPa range, which results in a reduction of microbial loads and thus extends the shelf life of the processed food. Under HPP, natural flavors can be retained to provide food of superior quality and nutritional value. All food-processing techniques must conform to sanitation and safety-related specifications before they can be employed in food and commercially applied. The pasteurization settings and control of conventional thermal processing techniques have been practically applied. Furthermore, appropriate heat-resistant strains can be selected as target microorganisms to verify the sanitation and ensure effective food safety. However, HPP is still an emerging processing technique, necessitating further investigation of its related scientific theories, parameter standards, and commercial applications. Therefore, the scientific theories behind HPP should be fully understood before appropriate parameter conditions such as pressure, temperature, time, and pH can be accurately selected. Among these, the pressure-resistant characteristics of various microorganisms, as well as their potential physiological response to HPP, are key factors that must be considered when developing HPP foods. As reviewed in this paper, the pressure-resistant characteristics of microorganisms can facilitate the selection of target microorganisms, which can provide a reference for setting pasteurization conditions during food HPP, and reduce the possible unanticipated food safety issues caused by microorganisms after HPP.