Germin-like proteins (GLps) are a diverse and ubiquitous family of plant glycoproteins belonging to the cupin super family; they play considerable roles in plant responses against various abiotic and biotic stresses. Here, we provide evidence that GLP2 protein from cotton (Gossypium hirsutum) functions in plant defense responses against Verticillium dahliae, Fusarium oxysporum and oxidative stress. Purified recombinant GhGLP2 exhibits superoxide dismutase (SOD) activity and inhibits spore germination of pathogens. Virus-induced silencing of GhGLP2 in cotton results in increased susceptibility to pathogens, plants exhibited severe wilt on leaves, enhanced vascular browning and suppressed callose deposition. transgenic Arabidopsis (Arabidopsis thaliana) plants overexpressing GhGLP2 showed significant resistance to V. dahliae and F. oxysporum, with reduced mycelia growth, increased callose deposition and cell wall lignification at infection sites on leaves. The enhanced tolerance of GhGLP2-transgenic Arabidopsis to oxidative stress was investigated by methyl viologen and ammonium persulfate treatments, along with increased H 2 o 2 production. further, the expression of several defense-related genes (PDF1.2, LOX2, and VSP1) or oxidative stress-related genes (RbohD, RbohF) was triggered by GhGLP2. Thus, our results confirmed the involvement of GhGLP2 in plant defense response against Verticillium and Fusarium wilt pathogens and stress conditions. Cotton (Gossypium hirsutum L.) is an important fiber crop that is considered the backbone of the global fiber economy 1. Verticillium and Fusarium wilt are caused by Verticillium dahliae and Fusarium oxysporum, respectively, which are soil-borne pathogenic fungi that present major constraints to the production of cotton 2. Verticillium wilt is a notorious and devastating disease of cotton 3 , and it occurs before the squaring stage and peaks in the boll-setting stage, causing necrotic areas on the leaves, wilting, and discoloration of the vascular tissues 4. The disease symptoms of Fusarium wilt initiate and peak at the seedling and squaring stages, respectively, showing necrotic patches between the main veins and leaf detachment from the stem 5. Due to diverse factors, such as the climate, pathogen population structures, and cultivar susceptibility, the currently available control measures for these two diseases are not adequate 6. Thus, research on the cultivation of resistant cotton plants, by finding novel disease-resistant genes against these soil-borne fungal species, is consequently, of great importance. Previous studies have suggested that extracellular germins and germin-like proteins (GLPs) could be induced by a range of abiotic or biotic stresses, such as herbivores 7,8 , drought 9,10 , salinity 8,11 and they are considered to be the pathogenesis-related proteins (PRs) 16 family due to their disease resistance property 12-14. Germins and GLPs were first characterized in wheat (Triticum aestivum) and constitute a large plant gene family 15. They occur as water-solub...