Integrating single-crystalline two-dimensional (2D) semiconductors onto silicon is critical to achieving the convergence of 2D materials with silicon (Si) lines. Compared with transfer, direct growth of 2D semiconductors on silicon offers benefits such as process compatibility with mainstream Si technology and the ability to form clean and uniform heterointerfaces. However, the direct growth of single-crystal 2D semiconductors on silicon is usually challenged by weak interfacial interactions and uncontrolled chemical reactions. Herein, we demonstrate an epitaxial integration strategy to grow single-crystalline 2D semiconductors on a Si (100). Through introducing a SrTiO3 buffer layer, which mitigates detrimental side reactions and offers excellent lattice match, successful coherent epitaxy of a single-crystal Bi2O2Se film on silicon has been achieved. The as-synthesized Bi2O2Se film exhibits outstanding single crystallinity and uniformity on a centimeter scale. Furthermore, transistors fabricated on 2D Bi2O2Se revealed a high field-effect mobility of up to ∼230 cm2 V-1 s-1. Our work provided a superior strategy for scalable preparation of high-quality 2D semiconductors on industrialized Si substrates.