Background <p>Hypopharyngeal cancer (HPC) is associated with a poor prognosis, often attributed to advanced staging and physiological frailty. However, the prognostic impact of psychological distress remains under-investigated. This study aimed to evaluate the predictive value of the NCCN Distress Thermometer (DT) for 5-year survival and identify early mortality predictors through longitudinal monitoring.</p> Methods <p>We retrospectively analyzed 80 patients with newly diagnosed HPC. Baseline and longitudinal DT scores, the NCCN Problem List, and objective physiological markers (BMI, Hemoglobin, CRP, and WBC) were collected. Survival outcomes were analyzed using Kaplan-Meier curves and the log-rank test. The association between distress trajectories, clinical stages, and physiological parameters was assessed.</p> Results <p>Among the 80 patients evaluated longitudinally, psychological burden shifted notably over the course of the disease. Initial baseline Distress Thermometer (DT) scores were unexpectedly low at diagnosis, even in advanced disease (mean 1.30 in Stage IV). However, distress escalated during active treatment, with peak DT scores reaching 2.62 in Stage III and 2.55 in Stage IV. Peak distress severity did not correlate with anatomical tumor stage (Spearman’s <i>p</i> = 0.488). Notably, patients who developed severe distress (peak DT ≥ 4) exhibited a significantly poorer 5-year overall survival (6.1% vs. 36.4%, <i>p</i> &lt; 0.05). Multivariate analysis confirmed that acute nervousness remained an independent prognostic factor for mortality.</p> Conclusions <p>Psychological distress in hypopharyngeal cancer patients is not static; it often begins low at diagnosis but peaks significantly during active treatment. Because severe distress and acute nervousness act as independent predictors of poor survival, a single baseline assessment is insufficient. Continuous longitudinal psychological screening and early intervention are essential to optimize patient outcomes.</p>