Silica has become a common platform for various catalytic and chemical reactions, biosensor, and drug release owing to its low toxicity, chemical and physical stabilities, large surface area, tunable pore sizes, and well-defined surface chemistry. Therefore, biomolecules encapsulated within a porous silica host has provoked significant interest in the development, application, and market of silica-based biosensors due to its potential application in analytic chemistry and biological science. Considerable progresses have been achieved in past few decades. This review focuses primarily on such advances in synthesis and applications of silica-based biosensors, especially emphasizing development which has occurred in the last 10 years, further driving readers to understand and construct various silica-based biosensors with high sensitivity and high stability.