Varroa destructor is an ectoparasite of honey bees and an active disease vector, which represents one of the most severe threats for the beekeeping industry. This parasitic mite feeds on the host’s body fluids through a wound in the cuticle, which allows food uptake by the mother mite and its progeny, offering a potential route of entrance for infecting microorganisms. Mite feeding is associated with saliva injection, whose role is still largely unknown. Here we try to fill this gap by identifying putative host regulation factors present in the saliva of V. destructor, and performing a functional analysis for one of them, a chitinase (Vd-CHIsal), phylogenetically related to chitinases present in parasitic and predatory arthropods, which shows a specific and very high level of expression in the mite’s salivary glands. Vd-CHIsal is essential for effective mite feeding and survival, since it is apparently involved both in maintaining the feeding wound open and in preventing host infection by opportunistic pathogens. Our results show the important role in the modulation of mite-honey bee interactions exerted by a host regulation factor shared by different evolutionary lineages of parasitic arthropods. We predict that the functional characterization of Varroa sialome will provide new background knowledge on parasitism evolution in arthropods and the opportunity to develop new bioinspired strategies for mite control based on the disruption of their complex interactions with a living food source.