Pathogens secrete effector proteins to suppress host immunity, mediate nutrient uptake and subsequently enable parasitism. However, on non-adapted hosts, effectors can be detected as non-self by host immune receptors and activate non-host immunity. Nevertheless, the molecular mechanisms of effector triggered non-host resistance remain unknown. Here, we report that a small cysteine-rich protein PstSCR1 from the wheat rust pathogen Puccinia striiformis f. sp. tritici (Pst) activates immunity in the non-host solanaceous model plant Nicotiana benthamiana. PstSCR1 homologs were found to be conserved in Pst, and in its closest relatives, Puccinia graminis f. sp. tritici and Puccinia triticina. When PstSCR1 was expressed in N. benthamiana with its signal peptide, it provoked the plant immune system, whereas no stimulation was observed when it was expressed without its signal peptide. PstSCR1 expression in N. benthamiana significantly reduced infection capacity of the oomycete pathogens. Moreover, apoplast-targeted PstSCR1 triggered plant cell death in a dose dependent manner. However, in Brassinosteroid insensitive 1-Associated Kinase 1 (SERK3/BAK1) silenced N. benthamiana, cell death was remarkably decreased. Finally, purified PstSCR1 protein activated defence related gene expression in N. benthamiana. Our results show that a Pst-secreted protein, PstSCR1 can activate surface mediated immunity in non-adapted hosts and contribute to non-host resistance.