Salicylic acid (SA) is an important signaling substance that plays an important role in plant growth, development and disease resistance. In order to further understand the role of the SA pathway in potato disease resistance and identify SA signaling key genes, gene expression profiling of the late blight resistance genotype SD20 was performed under exogenous SA application. A total of 28572 unigenes were assembled, of which 4564 were differentially expressed. Analysis of differentially expressed genes (DEGs) showed that multiple signaling pathways such as SA, jasmonic acid, ethylene, abscisic acid, auxin, and brassinolide were involved in response to exogenous SA. Many plant defense signal-related genes involved in protein serine/threonine kinase activity and plant-pathogen interaction, were significantly enriched. These were consistent with the interaction results of SD20 and Phytophthora infestans in our previous study, indicating that exogenous SA stimulated the resistance response and initiated a similar defense pathway compared to pathogen infection in SD20, which confirmed crosstalk of the SA signaling pathway with a pathogen-induced disease resistance signal pathway in plant. Moreover, transcriptome analysis revealed that ROS1 was positively regulated by SA in potato for the first time. SA-induced gene expression profiling provides insight into SA signaling and its mechanisms in disease defense systems.