Electronic patient-reported outcomes (ePROs)-based cancer symptom management presents an opportunity to improve patient outcomes by optimizing symptom detection and prompting clinician interventions in tertiary hospitals. However, real-world evidence is limited, especially in primary health care (PHC) settings, which are accompanied by more complex and unknown influencing factors.We conducted a qualitative study to identify facilitators and barriers associated with the implementation of ePRO-based symptom management in China's PHC settings under the implementation science (IS) framework. We further developed strategies and recommendations for real-world practices and health policies.This qualitative study was conducted from October to December 2023 in 9 purposively selected PHC institutions (5 urban and 4 rural) across 5 administrative districts of Yangzhou, Jiangsu Province, China. Community-dwelling patients with cancer, PHC providers, and medical supervisors participated in semistructured interviews and focus group discussions. We used 2 subframeworks under the IS framework-the Consolidated Framework for Implementation Research and Expert Recommendations for Implementing Change-to conduct data analysis and generate strategies.A total of 72 individuals were invited to participate in this study, including 35 community-dwelling patients with cancer (median 66, IQR 60-71.5 years; n=21, 60% men) and 23 PHC personnel (median 45, IQR 27-51 years; n=12, 52.17% men) who participated in semistructured interviews, and 14 medical supervisors (median 47.5, IQR 36.5-54 years; n=10, 71.43% men) who participated in focus group discussions. This study identified 29 barriers and 21 facilitators, and then developed 13 strategies. Crucial challenges include PHC providers' low self-efficacy and unclear role identification, coupled with community-dwelling patients' mistrust of primary care, cancer stigma, and fatalistic beliefs, which further reduce motivation; poor integration of ePRO with existing workflows and the absence of performance incentive mechanisms; a lack of nationwide standardized implementation guidelines and quality evaluation criteria; and outdated medical equipment and a limited range of medications. Common challenges included weak collaborative relationships and insufficient funding.Grounded in the IS framework, our study identifies 3 critical priorities for implementing ePRO-based cancer symptom management in PHC settings, including addressing individual-level motivational deficiencies among community-dwelling patients with cancer and PHC providers by resolving misconceptions, bridging knowledge gaps, and establishing supportive incentives; developing supportive medical partnerships and advancing tiered management systems to empower PHC settings; and creating standardized operational guidelines with clear workflows and implementing real-world data-driven regulatory feedback mechanisms to ensure quality control.©Min Li, Jingyu Zhang, Jundi Zheng, Changjin Wu, Zuting Shao, Cheng Lei, Hongfan Yu, Lu Xu, Yu Zhang, Xu Wang, Jin Bai, Qiuling Shi, Xiaojun Dai. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.10.2025.