Although hybrid proline-rich proteins (HyPRPs) are ubiquitous in plants, little is known about their roles other than as cell-wall structural proteins. We identified the geneHyPRP1inCapsicum annuumandNicotiana benthamiana, which encodes a protein containing proline-rich domain and eight-cysteine motif (8CM) that is constitutively expressed in various organs, mostly in the root, but is down-regulated upon inoculation with either incompatible or compatible pathogens. Ectopic expression ofHyPRP1in plants accelerated cell death, showing developmental abnormality with down-regulation of ROS-scavenging genes, and enhanced pathogen susceptibility suppressing expression of defense-related genes. Conversely, silencing ofHyPRP1suppressed pathogen-induced cell death, but enhanced disease resistance, with up-regulation of defense-related genes and inhibition ofin plantagrowth of bacterial pathogens independently of signal molecule-mediated pathways. Furthermore, the secreted 8CM was sufficient for these HyPRP1 functions. Together, our results suggest that a common plant cell-wall structural protein, HyPRP1, performs distinct dual roles in positive regulation of cell death and negative regulation of basal defense against pathogen.