Citrus Tristeza Virus (CTV), which colonizes phloem-associated cells in the infected citrus trees, continuously causes severe losses of the citrus crop worldwide. Dissecting the host immune response against virus infection would provide essential insights to develop effective management strategies. Recently, we found that the p33 protein encoded in the CTV genome is a viral effector and one of the pathogenicity determinants. In this work, p33 was used as a molecular bait to explore virus interactions with the host immunity. We found that citrus miraculin-like protein 2 (MLP2), a member of the Kunitz-type soybean trypsin inhibitor family, interacts with the viral p33 protein. Upon expression, MLP2 localizes to the endoplasmic reticulum and the Golgi apparatus and induces cellular stress and accumulation of the reactive oxygen species. Interestingly, the oxidation-related function of MLP2 relies on its N-terminal signal peptide, but not the Kunitz motif. Binding of MLP2 interrupts the cellular distribution of p33 whose proper function is necessary for the effective virus movement throughout the host. The overexpression of MLP2 from the virus dramatically reduced the infectivity of CTV in a plant host. Altogether, our data demonstrate that citrus MLP2 hijacks the viral movement-associated p33 protein and induces cellular oxidative stress to mount a defense against CTV infection.