Phytophthora capsici causes blight disease on over 50 crop species including tomato and pepper with annually multi-billion-dollar losses in crop production. P. capsici secret hundreds of effectors into a host cell to manipulate host immunity for successful colonization. However, even with the numerous studies on the roles of RXLR effectors, the molecular mechanisms of effector-induced necrotic host cell death remain elusive. Here, we report a novel P. capsici effector, Pc12, that causes cell death in the Solanaceae family without induction of defense-related gene expression and association with downstream signaling components of effector-triggered immunity. Pc12 enhances the colonization of P. capsici upon transient expression in Nicotiana benthamiana. Moreover, its homologs from other Phytophthora spp. having structural similarity with Pc12, especially in the C-termini, also induce cell death in N. benthamiana. Proteomics and microscopy assay reveal that Pc12 targets small GTPase Rab protein and perturbs vesicle trafficking between ER and Golgi apparatus, suggesting that the expression of Pc12 results in cell death under severe ER stress. Together, our results imply a new effector family functions in their pathogen growth via ER-mediated cell death.