Sorbus commixta Hedl. (Rosaceae) is a well-known herbal tree. Its fruit, commonly called the rowanberry, is traditionally eaten for refreshment and has been used as a laxative and as a gargle for sore throats. We explored the novel pharmacological activity of the S. commixta fruit and found that its ethanolic extracts reduced the viability of human lung adenocarcinoma cells by inducing apoptotic cell death in a p53-independent manner. Column chromatographic separation of the ethanolic extract led to isolation of three main constituents, benzyl beta-D-glucopyranoside, sambunigrin, and prunasin. This is the first report showing the presence of the cyanogenic glycosides, sambunigrin and prunasin, in S. commixta fruit. These findings provide experimental evidence for a novel biological activity of S. commixta fruit against human lung cancer cells and identification of the main constituents, which raise the potential of using S. cornmixta fruit as a functional food for tumor prevention and management.