Purpose: This study aimed to evaluate the effects of acupressure on pain, anxiety, depression, and physiological parameters in women undergoing brachytherapy for gynecological cancer. Methods: The research was conducted between December 2023 and September 2024 using a randomized controlled design. All patients receiving brachytherapy were randomly assigned to the acupressure group (n = 40) or the control group (n = 40). In addition to standard clinical care, the acupressure group received manual acupressure for 30 min before each brachytherapy session at specific acupressure points (SP6, PC6, LI4, HT7, LV4). The data were collected using the Personal Information Form, Visual Analog Scale (VAS), State-Trait Anxiety Inventory (STAI-I), Hospital Anxiety and Depression Scale (HADS), and Vital Signs Form. Results: The groups were comparable in terms of sociodemographic and clinical characteristics (p > 0.05). Significant reductions were observed in anxiety, depression, and pain levels in the acupressure group at post-test compared to baseline and the control group (p < 0.001). Additionally, diastolic blood pressure and body temperature significantly decreased in the intervention group (p < 0.001), whereas no significant differences were found for pulse and respiratory rate (p > 0.05). Conclusion: The results obtained from this study suggest that acupressure may be a beneficial complementary method for reducing anxiety, depression, and pain, as well as contributing to the regulation of certain physiological parameters in patients undergoing brachytherapy. These findings indicate that acupressure could be considered an intervention that may be integrated into clinical practice to support psychological and physiological well-being. Trial registration: NCT06531551. Date of Registration: 1 August 2024.