Schizophrenia is a common type of serious mental illness with an unclear etiology. Recently, the excessive production of hydrogen sulfide in the brain has been considered to be one of the pathophysiological bases of schizophrenia. However, due to the existence of the blood-brain barrier (BBB), almost no fluorescent probe has been successfully used for the sensing and detection of H2S in the brain. Herein, we designed and synthesized a series of near-infrared fluorescent probes SiR-Bs based on a hemicyanine and Si-rhodamine structure. Among them, Mindo-SiR presented a good penetration ability of the BBB, a high brain uptake (transport: 4.95% ID/g at 5 min), and good response to H2S in vitro and in vivo. For the first time, a fluorescent probe was used to image the changes of H2S in the brains of schizophrenic (SZ) mouse models, and it was successfully proven that there was an abnormally high level of H2S in the brains of SZ mice. Moreover, the therapeutic effect of risperidone for the treatment of SZ could be evaluated by the changes of SiR-Bs' fluorescence imaging.