The purpose of this study is to evaluate the feasibility and diagnostic performance of 18F-PSMA PET/CT-ultrasound (PET/CT-US) or PET/MRI-ultrasound (PET/MRI-US) fusion targeted biopsy for intra-prostatic PET-positive lesions. 55 candidates were prospectively enrolled for PET/CT-US or PET/MRI-US fusion targeted biopsies at solitary PET-positive lesions. A total of 178 core biopsies were performed on 55 patients. 146 biopsy cores (82.0%, 146/178) from 51 (92.7%, 51/55) patients were positive for prostate cancer; 47 (85.5%, 47/55) were clinically significant prostate cancer. 18F-PSMA PET/CT-US or PET/MRI-US fusion-targeted prostate biopsy are feasible for prostate cancer diagnosis and has high detection rate of clinically significant prostate cancer.