Psoriasis is an erythrogenic skin condition identified by multi-layered scales in addition to the thick epidermis (top layer of the skin). The function of interleukin-17A (IL-17A) in the progression of psoriasis is well-known. The interactivity of IL-17A with IL-17(R)A is the main target to investigate the interaction between the two interleukins, which resulted in the amelioration of psoriasis in mice. Our study was aimed to analyze the PCA effects on the association between IL-17A and IL-17(R)A in psoriasis induced mouse model by imiquimod (IMQ). The topical use of IMQ caused psoriasis in mice, followed by oral administration of two doses of PCA (-50 and -100 mg/kg) respectively for fourteen successive days. IL-17A blocking assay was performed to analyze the relationship between IL-17A and IL-17(R)A, followed by RNA-sequencing and histopathological studies. The blocking assay of IL-17A demonstrated that PCA was able to interrelate with the IL-17A residues and therefore eliminated the binding capacity of IL-17(R)A to IL-17A. PCA, in a dose-dependent manner, changed the interrelationship between IL-17A and IL-17(R)A; diminished IMQ-caused mice's skin lesions, and also improved histopathological lesions. PCA diminished the invasion of the inflammatory cells and cytokine secretions in IMQ-treated psoriasis. Our results identified novel findings involving oral administration of protocatechuic acid as a bioactive compound that offered protection against IMQ-caused psoriasis in mice through the alteration of interaction between interleukin-17A and IL-17(R)A.