Abstract: Certain infants and children have relatively high risk of the onset of anaphylaxis when exposed to the foods containing cow milk protein. This pathogenic immunological process is mainly mediated by IgE. Currently, the chief methods eliminating the sensitization of milk protein include heat treatment, high pressure treatment, enzymatic hydrolysis, and glycosylation modification, etc. Based on different mechanisms, each technique has specific advantages, nevertheless, also accompanied with ineluctable shortcomings, such as reducing the nutritional value or generating odd flavors. As a type of secondary metabolites with wide botanical resources, polyphenols exhibit pleiotropic bioactivities involving anti-aging, antibiosis, anti-inflammation and antioxidation. It is well known that polyphenols have strong affinity to proteins via covalent or non-covalent binding, which is so-called 'polyphenol-protein interaction (PPI)'. Accumulating reports showed that phenolic compounds could reduce the immunoreactivity of diverse food allergens through PPI. This review summarizes and discusses the role of PPI on the desensitization of lactoproteins, and proposed some promising conceptions in the light of up-to-date researches, hoping to provide new ideas and theoretical foundations for the development of safe dairy products of low-sensitization.