Background <p>Early identification and timely intervention of radiotherapy‑related toxicities are crucial for maintaining treatment adherence and improving quality of life in patients with head and neck cancer (HNC) undergoing concurrent chemoradiotherapy (CCRT). To address this clinical need, a nurse‑led smartphone application, Sun Yat-sen Symptom Management (SYS-SM), was developed to integrate patient‑reported outcome (PRO) assessments with personalized self‑management guidance tailored to individual symptom profiles. The feasibility and preliminary efficacy of this application were evaluated in a randomized controlled trial (RCT).</p> Methods <p>Eligible patients were randomly assigned to an intervention group or a control group. During the 3-month intervention period, the intervention group received standard care combined with nurse-led personalized mobile symptom management, whereas the control group received standard care alone. The intervention included in-person discharge education, structured instruction on application use, and automated push notifications delivering individualized health management recommendations based on PRO data. When symptom scores exceeded predefined thresholds, alerts were automatically generated for nursing staff. Clinical outcomes were assessed at baseline (T0), 1 month (T1), and 3 months (T2).</p> Results <p>A total of 136 patients were enrolled (107 [78.7%] men; mean [SD] age, 50.88 [12.6] years), including 67 participants in the intervention group and 69 in the control group, with no significant differences in baseline characteristics. For health-related quality of life (HRQOL), the primary summary scores showed no significant overall group × time interaction <i>(P</i> = 0.108; T2: mean difference [MD] = 4.61; 95% CI, -1.02–10.24; effect size [ES] = 0.23). In the physical functioning domain demonstrated a significant interaction effect (<i>P</i> = 0.048; T2: MD = 8.25; 95% CI, 1.15–15.35), its effect size (ES = 0.35) remained below the clinical threshold (ES ≥ 0.40). Notably, significant improvements were observed in several secondary domains, specifically appetite loss (interaction <i>P</i> = 0.001; ES = -0.56) and global health status (interaction <i>P</i> = 0.009; ES = 0.46). Improvements in self-efficacy (SUPPH interaction <i>P</i> = 0.012) and psychological status (IDA interaction <i>P</i> &lt; 0.01) were significantly greater in the intervention group. The SYS-SM application demonstrated high feasibility and acceptability.</p> Conclusions <p>A nurse-led personalized mobile health symptom management intervention did not significantly improve primary overall HRQOL summary scores, but it demonstrated targeted benefits in reducing specific symptoms (particularly appetite loss), enhancing self-management capacity, and alleviating negative affect in patients with HNC undergoing concurrent chemoradiotherapy. The application shows potential for broader clinical implementation.</p> Trial registration <p>The study was prospectively registered with the Chinese Clinical Trial Registry (ChiCTR2300072314) on June 9, 2023.</p>