Proteases have the advantages of high catalytic efficiency and strong specificity, which are widely used in food, chemical, medicine and other industrial fields. However, natural proteases are susceptible to environmental acidity and inappropriate environmental acidity reduces their catalytic efficiency. Effective strategies to improve the acidity resistance of enzymes are key to promote their industrial application. Rational design strategy is an effective technique to improve the acidic stability of enzymes, such as homologous sequence alignment, surface charge optimization, and intramolecular force optimization. Considering most foods and food raw materials which are subject to contamination by ochratoxin A (OTA) are acidic, this review summarizes the common strategies for improving the acidic stability of enzymes and their prospects for application in the field of OTA degradation. It is expected that this review will provide a reference for research on the acid resistance of industrial enzymes and provide a theoretical basis for the application of mycotoxin-degrading enzymes.