Objective:To establish a novel clinical application process of the optical surface monitoring system (OSMS) in the cranial frameless stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT), and to assess the accuracy and effectiveness of the OSMS in the intra-fraction motion monitoring of both cranial phantoms and cranial SRT patients fixed using the Q-Fix encompass immobilization system.Methods:The deviations of OSMS in the real-time motion monitoring were assessed by determining the deviations between the displacement of the cranial SRS phantoms detected by the OSMS and the predefined displacement of the Varian Edge six degrees of freedom (6DoF) couch. The ability of the OSMS to conduct real-time monitoring of the head movement was also analyzed when one camera was blocked by the rotary gantry of the accelerator and when the couch was at non-zero angles. Moreover, ten patients who received 50 fractions of cranial frameless SRT were enrolled in this study. All the patients were fixed using the Q-Fix Encompass system, and their intra-fraction motion was monitored using the OSMS. The intra-fraction errors of OSMS real-time monitoring throughout the treatment were obtained from the OSMS logs. The patients received cone-beam computed tomography (CBCT) after the beam delivery, and the six-dimensional errors were obtained as intra-fraction motion errors of the CBCT.Results:For the cranial phantoms, there was a close correlation between the OSMS monitoring deviations and the predefined displacement in six dimensions. The OSMS-detected 3D vector deviations in the translational and rotational directions were (0.28±0.10) mm and (0.15±0.09)°, respectively when the angel both the gantry and couch was 0° and were (0.35±0.13) mm and(0.17±0.09)°, respectively, when one camera was blocked. The OSMS monitoring deviations with the couch at a non-zero degree were greater than those at zero degree. The maximum deviations occurred when the couch was at 270° and were (0.69±0.19) mm and (0.32±0.12)°, respectively, in the translational and rotational directions. For the cranial SRT patients fixed using the Q-Fix Encompass system, the OSMS and CBCT showed comparable intra-fractional motion deviations, which were (0.40±0.26) and (0.29±0.10) mm, respectively in the translational direction and were (0.33±0.20)°and (0.26±0.08)° in the rotational direction.Conclusions:The OSMS is an effective tool for optically guided radiotherapy, which allows for intra-fraction real-time motion monitoring with sub-millimeter accuracy. Therefore, to ensure the accurate preformation of cranial SRS/SRT, it is necessary to conduct the intra-fractional position monitoring using OSMS.