Background: The purposes of this study are to explore risk factors for disease progression during primary treatment, and to analyze disease prognosis of different event groups in a historical cohort of 56 pediatric patients with head and neck rhabdomyosarcoma.Methods: From June 1st, 2016 to June 30th, 2019, a historical cohort of 56 pediatric patients diagnosed as head and neck rhabdomyosarcoma was chosen. Clinical data were collected including general information about diagnosis, treatment, prognostic factors, and follow up results. Patients were divided into non-event group, disease-progression group and disease-relapse group according different types of events. Comparison among the three groups was made to reveal different clinical features and prognosis. Patients were further divided into disease-progression group and non-progression group to explore risk factors for disease progression, with univariate and multivariate analysis.Results: The median follow-up time of all 56 patients was 31.8 months (range 3.5-74.6 months). There were 30 non-event patients, 12 disease relapse patients, and 14 disease-progression patients. The estimated 5-year overall survival rates were 100.0%, 82.5%, and 11.9% for non-event, disease-relapse and disease-progression patients respectively (p<0.001). Compared with non-event patients, disease-progression patients had higher rates of tumor size>5cm (p=0.008) and non-initial radiation therapy (p=0.001). Compared with disease-relapse patients, disease-progression patients had a higher rate of tumor size>5cm (p=0.002), and higher ranks of surgical-pathologic group (p=0.009) and risk group (p<0.001). Compare with non-progression patients, univariate analysis demonstrated that tumor size>5cm, alveolar histology, non-initial radiation therapy, and higher ranks of surgical-pathologic group as well as risk group were statistically significant risk factors for disease progression. The multivariate analysis result showed tumor size>5cm (OR=6.75, 95%CIs 1.02-44.78), alveolar histology (OR=7.10, 95%CIs 1.08-46.57), and non-initial radiation therapy (OR=15.26, 95%CIs 2.38-97.70) to be independent risk factors for disease progression.Conclusions: Pediatric head and neck rhabdomyosarcoma patients with disease progression have significantly worse overall survival, and the prognosis is obviously different from patients with disease relapse and patients without events. Tumor size>5cm, alveolar histology and non-initial radiation therapy are independent risk factors for disease progression. Patients with disease progression tend to have higher ranks of surgical-pathologic group and risk group.