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Abstract Background Palliative care (PC) is an approach that improves the quality of life (QoL) of patients and their families facing the problem associated with incurable terminal disease. A number of QoL assessment tools have been validated in PC and their use described for research purposes, to support clinical practice, and as part of the quality improvement programs. There is a paucity of evidence on the implementation of a nursing intervention focused on QoL assessment in PC practice. The aim of this study is to model and determine the feasibility of a nursing complex intervention focused on QoL assessment in PC practice. Methods The intervention will be evaluated through a quasi-experimental non-equivalent comparison group before-after study design. This project can be classified as phases 1–2, according to the Medical Research Council (MRC) framework for the development and evaluation of complex interventions. The study setting will take place in two inpatient hospice units in Italy. The study sample will be constituted of 39 multidisciplinary healthcare professionals and a sample of 46 advanced cancer patients admitted to hospices during the implementation of the intervention. Discussion This study will generate information to address the implementation of QoL measurement in palliative care practice. Findings of this study will be used to inform a phase 3 trial according to the MRC framework. Trial registration ISRCTN41201864 retrospectively registered.