Diaspis echinocacti (Bouché, 1833) (Hemiptera: Diaspididae) is a pest insect that can be responsible for gall formation in cactus (Cereus sp.). The process of gall formation in cactus is not fully understood, and there are few studies available on the interaction of D. echinocacti with the cactus plant. Therefore, the aim of this study was to identify morphophysiological changes in the tissues of Cereus sp. infested with D. echinocacti. We performed histological and ultrastructural analyses and UV/Vis spectrophotometry. Gall formation was only observed in plants infested naturally with D. echinocacti. During histological analysis of the gall samples, we observed the formation of a suber region, interspersed with parenchymal cells and cells with lignified walls. Additionally, there was an increase in xylem conductor bundles and an absence of palisade parenchyma cells. Physiologically, the levels of flavonoids in the gall tissues were reduced compared to those in the control. Our data suggest that D. echinocacti may plays a role in gall formation and triggers cellular and physiological changes in infested Cereus species.