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Actinic keratosis is a common, chronic, and potentially pre-cancerous skin disease that can negatively impact patients' health-related quality of life. This systematic review aimed to identify and describe the questionnaires used to assess health-related quality of life in patients with actinic keratosis and summarize reported impacts. Four databases (EMBASE, PsycINFO, PubMed, and Cochrane Library) were searched up to February 2025. Two reviewers independently screened articles, and risk of bias was assessed using tools appropriate to study design. Of 639 records, 37 studies including 9,326 patients met inclusion criteria. Most studies were interventional (59%) and of moderate to high quality (64%). Health-related quality of life was assessed using 3 disease-specific, 3 dermatology-specific, and 2 generic questionnaires. The most frequently used instruments were the Actinic Keratosis Quality of Life (n = 13) and the Dermatology Life Quality Index (n = 16). All questionnaires detected health-related quality of life impairment, especially during treatment. Actinic Keratosis Quality of Life identified patient subgroups with greater health-related quality of life reduction, including females, younger individuals, patients with comorbidities, and those with a history of skin cancer. All health-related quality of life questionnaires captured impairment in patients with actinic keratosis. The Actinic Keratosis Quality of Life and Dermatology Life Quality Index questionnaires were widely used. Actinic Keratosis Quality of Life identified subpopulations with health-related quality of life impairment. Among studies reporting mean health-related quality of life scores, the Dermatology Life Quality Index ranged from 1.55 to 24 and the Actinic Keratosis Quality of Life from 4.22 to 17, reflecting very broad variability and underlying differences in actinic keratosis severity across study populations.