Reduction of the overall treatment time (OTT) of radiotherapy results in increased T-site control in squamous cell carcinomas of the head and neck (HNSCC). However, the response is heterogeneous and accelerated repopulation of clonogenic tumour cells during therapy may be one of the factors determining this response. The aim of the present study was to identify the influence of the epidermal growth factor receptor (EGFr) and E-cadherin for T-site control when the OTT was reduced and whether the markers add information to the histopathological grading in selecting patients for accelerated radiotherapy. A total of 209 patients from randomized DAHANCA-trials with supraglottic larynx squamous cell carcinomas treated with primary radiotherapy with different OTT of 9(1/2), 6(1/2), and 5(1/2) weeks. Available formalin-fixed paraffin embedded tumour tissues were re-evaluated for histopathological characteristics and stained for EGFr and E-cadherin. Data were correlated with patient and tumour characteristics and 5-year T-site control. EGFr and E-cadherin were not associated with patient or tumour characteristics except that EGFr correlated to carcinomas with a well to moderate histopathological feature. Tumours with high EGFr or low E-cadherin did benefit from reduced OTT, and the combination of the two (high EGFr and low E-cadherin) had the most significant acceleration of treatment effect, compared with tumours with other combinations of EGFr and E-cadherin expression. Tumours with high expression of EGFr and low expression of E-cadherin showed the most significant increase in T-site control when the overall treatment time of radiotherapy was reduced, and the markers may be useful for selecting patients who will benefit from accelerated radiotherapy.