[18F]ML-10 is a novel apoptosis radiotracer for positron emission tomography (PET). We assess the apoptosis response of intracranial tumor early after CyberKnife (CK) treatment by [18F]ML-10 PET imaging. 29 human subjects (30 lesions), diagnosed with intracranial tumors, underwent CK treatment at 14–24 Gy in 1–3 fractions, had [18F]ML-10 positron emission tomography/computed tomography (PET/CT) before (pre-CK) and 48 hours after (post-CK) CK treatment. Magnetic resonance imaging (MRI) scans were taken before and 8 weeks after CK treatment. Voxel-based analysis was used for the imaging analysis. Heterogeneous changes of apoptosis in tumors before and after treatment were observed on voxel-based analysis of PET images. A positive correlation was observed between the change in radioactivity (X) and subsequent tumor volume (Y) (r=0.862, p<0.05), with a regression equation of Y=1.018∗X−0.016. Malignant tumors tend to be more sensitive to CK treatment, but the treatment outcome is not affected by pre-CK apoptotic status of tumor cells; [18F]ML-10 PET imaging could be taken as an assessment 48 h after CK treatment