INTRODUCTION: Due to the limitations of relying on randomised controlled trials, the potential benefits of real-world data (RWD) in enriching evidence for health technology assessment (HTA) are highlighted. Despite increased interest in RWD, there is limited systematic research investigating how RWD have been used in HTA. The main purpose of this protocol is to extract relevant data from National Institute for Health and Care Excellence (NICE) appraisals in a transparent and reproducible manner in order to determine how NICE has incorporated a broader range of evidence in the appraisal of oncology medicines. METHODS AND ANALYSIS: The appraisals issued between January 2011 and May 2021 are included following inclusion criteria. The data extraction tool newly developed for this research includes the critical components of economic evaluation. The information is extracted from identified appraisals in accordance with extraction rules. The data extraction tool will be validated by a second researcher independently. The extracted data will be analysed quantitatively to investigate to what extent RWD have been used in appraisals. This is the first protocol to enable data to be extracted comprehensively and systematically in order to review the use of RWD. ETHICS AND DISSEMINATION: This study is approved by the Ethics Committee of the London School of Hygiene and Tropical Medicine on 14 November 2019 (17315). Results will be published in peer-reviewed journals.