Objective: To compare the application value of perineal nerve block (PNB), prostate peripheral nerve block (PPB), and intrathecal anesthesia (IA) in the implantation of the gold fiducial marker (GFM) in image-guided radiotherapy for prostate cancer (PCa), and to explore the factor affecting the optimal pain control effect during nerve block surgery. Methods: 270 patients who received PCa IGRT and had GFM implanted in the Hospital of the PLA 81st Group Army from June 2018 to June 2023 were selected. Their clinical data for this prospective study was collected. The patients were randomly divided into PNB group, PPB group, and IA group by using the lottery method, with 90 cases in each group. Various clinical indicators during the perioperative period, visual analog scale (VAS), and incidence of adverse events (AE) among three groups of the patients were evaluated and compared. Multiple logistic regression analysis was used to identify the factors affecting VAS during the GFM implantation surgery for the optimal nerve block group. Results: After 5 minutes of the nerve block, the PNB group had the lowest mean arterial pressure (MAP) (P0.05), while the PPB group had the highest (P0.05). There was no statistically significant difference in various clinical indicators among the three groups during the surgery at other times (all P0.05). The VAS scores of PNB group were the lowest during the GFM implantation surgery and 6 hours after the surgery (all P0.05). There was no statistically significant difference in the incidence of AE among the three groups (P0.05). The result of multiple logistic regression analysis showed that, GFM location and perineal nerve branches were the independent risk factors affecting pain control effectiveness (all P0.05) for the optimal nerve block PNB group. The risk of VAS score ≥ 4 increased by 2.389 times and 1.592 times, respectively, when GFM was located at the bottom and superficial branch block of perineal nerve. Conclusion: GFM implantation nerve block PNB have the lowest perioperative MAP and the best pain control effect. PNB has certain clinical promotion and popularization significance. It is necessary to avoid the risk factors to ensure the application safety and clinical value before PNB.