In order to study the law of hydrogen leakage diffusion and fire spread in university laboratories, this paper uses computational fluid dynamics software to construct a full-scale three-dimensional simulation model of the laboratory to simulate the process of hydrogen leakage and fire development, and discusses the effects of different leakage apertures on hydrogen diffusion and combustion. The results show that when the leakage aperture is 5 mm, hydrogen only flows in the room where the leakage point is located and accumulates at the top, and a small-size jet flame is generated after hydrogen ignition. When the leakage aperture is 10 mm, hydrogen is still confined in the room at the leakage point, but the flame jet height increases after igniting hydrogen, which is easy to form a ceiling jet to destroy the roof structure. When the leakage aperture is 25 mm, the corridor becomes a diffusion channel, and hydrogen enters the opposite room. The height of the indoor jet flame further increases and directly impacts the ceiling. The high heat in the room also diffuses to the corridor, affecting the safe evacuation of personnel.