Parkinson's disease (PD) is a highly heterogeneous disorder that is difficult to diagnose. Therefore, reliable biomarkers are needed. We implemented a method constructing a regional radiomics similarity network (R2SN) based on the amplitude of low-frequency fluctuation (ALFF). We classified patients with PD and healthy individuals by using a machine learning approach in accordance with the R2SN connectome. The ALFF-based R2SN exhibited great reproducibility with different brain atlases and datasets. Great classification performances were achieved both in primary (AUC = 0.85 ± 0.02 and accuracy = 0.81 ± 0.03) and independent external validation (AUC = 0.77 and accuracy = 0.70) datasets. The discriminative R2SN edges correlated with the clinical evaluations of patients with PD. The nodes of discriminative R2SN edges were primarily located in the default mode, sensorimotor, executive control, visual and frontoparietal network, cerebellum and striatum. These findings demonstrate that ALFF-based R2SN is a robust potential neuroimaging biomarker for PD and could provide new insights into connectome reorganization in PD.