Sclerotinia wilt of sunflower caused by Sclerotinia sclerotiorum is a devastating disease causing serious loss. Selenium (Se) has a benefit effect to plant in stress tolerance. In this study, sunflower leaves treated by foliar application of Se were inoculated with S. sclerotiorum. Pathogenesis on the inoculated leaves and transcript levels of plant genes involved in redox homeostasis and hormonal signaling pathways were examined. Se could be detected after the foliar application and was mainly transformed to selenomethionine in sunflower. Consequently, Se pretreatment delayed the necrosis development caused by S. sclerotiorum and alleviated the adverse effects derived from pathogen infection by differentially balancing the regulation of enzymes involved in the redox homeostasis. Specially, the cat expression increased to alleviate its downregulation responded to pathogen infection at the earlier infection stage (12 hour post inoculation, hpi) while the pod, gpx, apx, and nox expressions decreased to alleviate their responsive upregulation at the later infection stages (24 and 36 hpi). Se pretreatment enhanced the regulation of genes involved in hormonal signaling pathways, in which the AOC and PAL expressions increased to enhance its upregulation induced by pathogen infection for improving resistant responses at the earlier infection stage (12 hpi), as well as the AOC and PDF expressions increased at the later infection stages (24 hpi). Besides, the EIN2 expression increased to alleviate its downregulation at all of infection stages. Our results suggested that Se plays the beneficial effect on the resistant responses to S. sclerotiorum infection. This study provided a clue to improve the sustainable management of Sclerotinia wilt on sunflower by Se foliar application.