Updated project metadata. Background: Cylindrocladium parasiticum Crous, Wingfield & Alfenas, the causal agent of Cylindrocladium black rot (CBR) of peanut (Arachis hypogaea L.), has leaded to economic losses in China. Learning about how peanut responds to C. parasiticum infection will be conducive to designing strategies for CBR control. However, the response of peanut plant to C. parasiticum is poorly understood. Results: In this study, two contrasting peanut cultivars, T09 (C. parasiticum-resistant) and P562 (C. parasiticum-susceptible) were used for comparative analysis of protein profiles in the root segment of peanut plants in responses to C. parasiticum infection. Proteomic profiling identified 1647 and 391 differentially expressed proteins (DEPs) in A. hypogaea L. P562 and A. hypogaea L. T09, respectively, compared to controls. A total of 350 and 1095 DEPs were identified between A. hypogaea L. P562 and A. hypogaea L. T09 before and after 9 dpi, respectively. Functional categorization by GO annotation showed that C. parasiticum-responsive proteins were mainly involved in catalytic activity and binding. The results of KEGG pathway analysis indicated both resistant and susceptible peanut cultivars can regulate gene expression in the phenylpropanoid pathway, terpenoid backbone biosynthesis, SA, and JA pathways to induce defensive genes and protein expression which enhances plant defence capacity. However, the MAPK signal pathway was more pronounced in resistant peanut cultivar T09. We also observed an increase of CYP73A100 involved in phenylpropanoid biosynthesis and flavonoid biosynthesis pathways in the susceptible peanut ecotype P562, while decrease in the resistant peanut ecotype T09, after 9 dpi. Additionally, there was a marked activation of brassinosteroid biosynthesis in the resistant T09, which indicated a possible involvement of activation of plant immune response in the resistant responses of peanut to C. parasiticum. Conclusions: This study provides some insights into the molecular networks involved on cellular and physiological responses to C. parasiticum infestation.