Background This present retrospective single center study was intended to investigate the factors associated with acute radiation oral mucositis or dermatitis during hypopharyngeal carcinoma radiotherapy.Methods From May 2012 to December 2018, previously untreated 93 patients with hypopharyngeal squamous cell carcinoma received radiotherapy in Affiliated Cancer Hospital of Zhengzhou University were enrolled. Radiation Therapy Oncology Group (RTOG) scoring criteria were used for assessing the severity of toxicities. Patients are therefore classified into “mild reaction group” (G0~G1) and “acute reaction group” (G2~G4). Single variate was applied to screen out factors with significant difference between mild and acute reaction groups, multivariate analysis was used to detect independent risk factors from those related. A total of 16 medical and laboratory indexes were included to examine, i.e., gender, age, smoking history, primary site, history of hypotension and diabetes, treatment modalities, dose, T (tumor) staging, N (reginal lymph node) staging, as well as hemoglobin value (1 week before radiotherapy). Relevant data used for the study were collected from clinical records.Results Total of 93 subjects completed radiotherapy. Acute mucositis occurred in 75 patients, and 27 cases developed acute radiation dermatitis. Smoking history, post-operative radiotherapy, concurrent chemotherapy, T staging, N staging, total dose (Gy) for GTV, single fraction dose (Gy) for GTV, and hemoglobin value (1 week before radiotherapy) showed significant differences between G0~G1 and G2~G4 groups of oral mucosa reaction; significant differences between mild and acute dermatitis reaction groups were found in diabetes history, hemoglobin value, age, total dose (Gy). Multivariate analysis showed that higher hemoglobin value ( OR = 1.120, P = 0.031), smoking history ( OR = 0.070, P = 0.031) were independent risk factor of acute OM; significant relationships for acute skin reaction were found with hemoglobin value ( OR = 1.059, P = 0.034) and older age ( OR = 1.068, P = 0.036).Conclusion Multivariate analysis showed higher hemoglobin value and smoking history to be the most relevant factors independently predicting grades 2 or higher OM; higher hemoglobin value and older age were found to be significantly associated with acute skin reaction.