Abstract: Trichoderma is a genus of filamentous fungi that are of interest to agriculture production and show good application prospects. Trichoderma interact with roots through signals, including colonization on the roots or as an endophyte of plants, regulating roots growth and plasticity, and promoting water and nutrients absorption. Trichoderma genomes contain a large number of biosynthetic gene clusters (BGCs) of natural active substances, which play a crucial role during Trichoderma-root interactions. Bioactivity-guided and genome mining isolation are the generally used methods to screen secondary metabolites (SMs) of Trichoderma, which usually are plant hormones and small molecule compounds. However, the screened SMs lack novelty in structures and encouraging researchs, and most known interactions are with model plantArabidopsis, limiting the basic theoretical breakthroughs in Trichoderma-root and application in agricultural production. It is urgent to incorporate theoretical breakthroughs of the screening study of new natural active products of Trichoderma into green agricultural development, which would be very important opportunities and challenges to achieve the sustainable agriculture in China.