Patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) have poor survival outcomes. The real-world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)-based chemoradiotherapy in patients with LA-HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3-year overall survival (OS) rate. Log-rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow-up time was 54.2 (95% confidence interval [CI]: 52.7-55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57-0.99, p = 0.038) and progression-free survival (PFS) (HR = 0.74, 95% CI: 0.58-0.96, p = 0.021). Subgroup analysis revealed that aged 50-60 year, IV, N2, radiotherapy dose >= 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab-related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA-HNSCC patients in an IMRT era.