Background: Nurse practitioners (NPs) are regarded as part of the primary healthcare professional team in rural hospitals, which often faced difficulties in hiring doctors. Only a few studies have been conducted that assess the barriers to practice for NPs in rural hospitals in Taiwan. Purpose: This study was designed to explore the barriers of practice for NPs working in rural hospitals. Methods: A qualitative research approach was used in this study, and participants were recruited using purposive sampling. Data on barriers to clinical practice were collected using face-to-face, in-depth interviews. Results: A total of 10 NPs participated in this study. The three barriers identified were patient safety concerns, the impact of limited medical resources and the demands and heavy workload on NPs, and the difficulties of balancing the interests of profit-oriented hospitals and patients' personal medical insurance rights. Conclusions/ Implications for Practice: To reduce barriers to practice, NPs require additional training from the government to strengthen their clinical knowledge and skills. In addition, when facing insufficient support from the Department of Health, these NPs may leverage online hospital marketing and crowdfunding platforms to obtain necessary software/hardware resources for their rural hospitals. If universal health insurance and personal medical insurance are misused within a hospital, NPs should have the moral courage to speak up and should be provided with adequate protection under rules and regulations that allow them to report cheating, illegal behaviors, and other activities that waste / misdirect healthcare resources.