Non-melanoma skin cancer (NMSC) is the most common neoplasm. The characteristics of this disease (location in aesthetically sensitive areas, the appearance of successive tumors during follow-up, and high rates of survival) are such that the concept of health-related quality of life (HRQoL) is of particular importance. The aim of the present study was to describe and analyses patient quality of life following diagnosis with cervicofacial NMSC. A descriptive cross-sectional study was conducted on patients with cervicofacial NMSC, confirmed by skin biopsy. In each case, when the definitive diagnosis of NMSC was established, the patient completed the Skin Cancer Index questionnaire and demographic data, health status, and sun exposure habits were recorded. The study population was composed of 220 patients with histologically confirmed cervicofacial NMSC. The mean score obtained for the Skin Cancer Index questionnaire was 54.1 (SD 21.9), in which the social-aesthetic component had a mean score of 76.7 (SD 26.2), while the emotional component had a mean score of 23 (SD 25.1). Male patients, those with secondary or higher education, and those who had no history of anxiety or depression had significantly higher mean scores for HRQoL. This study demonstrated that the diagnosis of cervicofacial NMSC significantly impacts HRQoL and that certain population groups (women, persons with only primary or no education qualifications, and those a history of anxiety or depression) are more susceptible. The questionnaire scores obtained were lower than those reported in previous studies on this topic and reflect a particularly strong impact on emotional aspects of patient quality of life.