The aim of the present study was to assess the quality of life (QoL) in patients undergoing surgical therapy for cancer of the lower region of the oral cavity (floor of the mouth and adjacent regions such as the tongue, alveolus, buccal sulcus, and oropharynx). A total of 83 patients were enrolled into the study. QoL was assessed using the core questionnaire and the head and neck module of the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30 and EORTC H&N35). The questionnaires were distributed to the patients preoperatively on the day of hospital admission and 3 months, 6 months and 12 months postoperatively. The changes in the scores were tested longitudinally for statistical significance using a repeated measures analysis of variance (ANOVA). The effect of gender, tumour stage, and prognosis (recurrent disease/non-survival) were tested at the individual intervals additionally by ANOVA procedures. Results showed that surgical treatment of oral cancer of the floor of the mouth led to a temporary deterioration of physical function and role function 3 months after surgery. These changes were accompanied by a significant decrease in oral function with reduced body image and reduced ability and willingness for social contact. The levels of these scores improved until the end of the first year after treatment. Pain, emotional function and the feeling of being ill constantly improved during 1 year. Patients with advanced stage of the disease (Stages III and IV) showed lower values in role function, social function, pain- and site-specific effects such as swallowing and nutritional aspects.