Nonsteroidal anti-inflammatory drugs (NSAIDs), including salicylic acid (SA), target human cyclooxygenases (COX) to block prostaglandin synthesis. In plants, SA functions as a key signaling molecule in the immune response to pathogens. Previously, we found that the oxicam-type NSAID tenoxicam (TNX) inhibits SA-dependent plant immune responses, accompanied by attenuation of NPR1 protein, a master regulator of SA-dependent signaling. However, the molecular target of TNX in plants remains largely unknown because plant genomes are not predicted to possess close homologs of the COX gene. Here, we report the target identification of TNX in plants. We identified a cupin domain-containing protein, CUPIN1, as a TNX interactor by a pull-down approach using TNX-immobilized beads. Genetic disruption of both CUPIN1 and its homolog CUPIN1h impairs immunity to bacterial pathogens and SA-induced accumulation of NPR1. Using transcriptomic analysis, we found that loss of both CUPIN1 and CUPIN1h significantly increases the expression level of UGT76B1 glycosyltransferase, an enzyme that converts immune-related signaling molecules (such as SA and N-hydroxypipecolic acid) into their respective inactive glucosides. In addition, TNX treatment up-regulates UGT76B1 expression in plants. The phenotypic similarity between the cupin1cupin1h double mutant and the TNX-treated plant suggests that CUPIN1 and CUPIN1h are molecular targets of TNX. We will discuss possible roles of CUPIN1 in plant immune signaling and the mode of action of TNX in plants.