IntroductionWith the worsening of population ageing globally, the number of the elderly with chronic and incurable diseases such as malignant tumours is gradually increasing, and the need for palliative care is growing. As a primary task in the end-of-life phase, symptom management is an essential aspect of palliative care, which aims to alleviate distressing symptoms of terminally ill patients and improve their quality of life. Virtual reality (VR) technology, which allows the creation of simulated environments in which a three-dimensional experience is generated, has been increasingly used in palliative care for symptom management. Therefore, we aim to conduct a systematic review to investigate the effects of VR-based interventions on end-of-life patients.Methods and analysisThis protocol for conducting a systematic review and meta-analysis will be prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. We will conduct a series of searches from inception to 31 July 2022 in the following databases: PubMed, Embase, Web of Science, the Cochrane Library, JBI, EBSCO, CNKI, Wanfang and SinoMed. The key concepts of ‘virtual reality’ and ‘end-of-life’ will be combined in each database using both free-text terms and controlled vocabulary terms (eg, MeSH/Emtree terms), if available. Two independent reviewers will use raw data to explore the effectiveness of VR for symptom management in end-of-life patients. The Cochrane Risk-of-Bias tool will be used to assess the risk of bias of included studies. Disagreements will be resolved by a third independent reviewer to reach a consensus. For the included articles, Review Manager software will be used for data synthesis and I2statistics will be used to measure the heterogeneity. Subgroup analyses and sensitivity analyses will be used to identify the source of heterogeneity.Ethics and disseminationAs this is a protocol for a systematic review and meta-analysis, patients will not be included in this study. For this reason, ethical approval is not required. In order to disseminate the research findings, the results and conclusions of this review will be submitted to a worldwide journal.PROSPERO registration numberCRD42022344679.