Abstract: The new flue-cured tobacco variety Guiyan21 is a male sterile hybrid variety developed with MSNC82 as the female parent and Fuyan3 as the male parent, with the aim of improving leaf quality, curing property, resistance to black shank disease, and the size of upper leaves. The variety was approved by the National Tobacco Variety Approval Committee in 2024. The variety tests conducted on Guiyan21 showed that it exhibited strong growth potential in the field, larger size of upper leaves, lower stem content ratio, easy curing, and resistance to black shank disease. Its appearance quality, chemical composition, and physical properties were similar with those of K326. With superior main economic traits and sensory quality to K326 and Yunyan 87. Guiyan 21 is suitable for planting in the southwestern tobacco growing area and is an excellent new variety that can balance industrial availability and tobacco farmers’ production benefits.