PURPOSE OF REVIEW: Two widely validated health-related quality of life (HR-QoL) tools, specifically designed for patients with advanced cancer, are the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL) and the Functional Assessment of Chronic Illness Therapy-Palliative (FACIT-Pal-14). This systematic review aims to evaluate the use of EORTC QLQ-C15-PAL and FACIT-Pal-14 in prospective studies in patients with advanced cancer, focusing on study types, clinical settings, additional HR-QoL tools used, and completion rates. RECENT FINDINGS: Sixty studies were included in the analysis. Both EORTC QLQ-C15-PAL and FACIT-Pal-14 are used in a variety of studies. Given that EORTC QLQ-C15-PAL was developed 9 years before FACIT-Pal-14 PAL, most studies utilized the EORTC tool. Both tools were shown to be successfully used in a variety of clinical settings, including in various advanced tumour types or different study designs, depending on the investigator and study needs. SUMMARY: This review demonstrates the wide range of utilization of EORTC QLQ-C15-PAL and FACIT-Pal-14 in prospective studies to assess the HR-QoL issues in patients with advanced cancers.