Introduction <p> Thrombocytosis, recognized as a clinically significant event, has been established as an unfavorable prognostic factor in various solid tumors. This study aimed to investigate the prognostic value of thrombocytosis—occurring either before or during treatment—in patients with non-metastatic nasopharyngeal carcinoma (NPC) who received intensity-modulated radiotherapy (IMRT).</p> Methods <p>A total of 203 patients with NPC who received IMRT were retrospectively analyzed. Thrombocytosis was defined as a platelet count exceeding 300 × 10⁹/L. The prognostic significance of thrombocytosis was assessed using the log-rank test and multivariate analyses.</p> Results <p>Among the 203 patients, 42 cases (20.7%) exhibited thrombocytosis prior to treatment initiation, and 81 cases (39.9%) developed thrombocytosis during therapy. Patients with thrombocytosis had more advanced N stage compared to those without (48.8% vs. 30.0%; P = 0.008). The 5-year progression-free survival (PFS) rate was significantly lower in patients with thrombocytosis than in those without (78.3% vs. 89.1%; P = 0.019). Multivariate analyses revealed that thrombocytosis was an independent prognostic factor for inferior PFS (hazard ratio [HR] = 2.37, 95% confidence interval [CI] = 1.08–5.21; P = 0.032). A similar result was observed in the subgroup of patients who received induction chemotherapy with the TP regimen (HR = 2.88, 95% CI = 1.12–7.36; P = 0.028).</p> Conclusions <p>Thrombocytosis occurring before or during treatment serves as a valuable predictor of disease progression and poor prognosis in patients with NPC. Patients presenting with thrombocytosis may require more intensive therapeutic strategies; therefore, the presence of thrombocytosis should be considered when selecting an induction chemotherapy regimen. Further prospective studies are warranted to confirm these findings.</p>