BACKGROUND: There is an increasing recognition that health intervention research requires methods and approaches that can engage with the complexity of systems, interventions, and the relations between systems and interventions. One approach which shows promise to this end is qualitative comparative analysis (QCA), which examines casual complexity across a medium to large number of cases (between 10 and 60+), whilst also being able to generalise across those cases. Increasingly, QCA is being adopted in public health intervention research. However, there is a limited understanding of how it is being adopted. This systematic review will address this gap, examining how it is being used to understand complex causation; for what settings, populations and interventions; and with which datasets to describe cases. METHODS: We will include published and peer-reviewed studies of any public health intervention where the effects on population health, health equity, or intervention uptake are being evaluated. Electronic searches of PubMed, Scopus, Web of Science (incorporating Social Sciences Citation Index and Arts & Humanities Citation Index), Microsoft Academic, and Google Scholar will be performed. This will be supplemented with reference citation tracking and personal contact with experts to identify any additional published studies. Search results will be single screened, with machine learning used to check these results, acting as a 'second screener'. Any disagreement will be resolved through discussion. Data will be extracted from full texts of eligible studies, which will be assessed against inclusion criteria, and synthesised narratively, using thematic synthesis methods. DISCUSSION: This systematic review will provide an important map of the increasing use of QCA in public health intervention literature. This review will identify the current scope of research in this area, as well as assessing claims about the utility of the method for addressing complex causation in public health research. We will identify implications for better reporting of QCA methods in public health research and for reporting of case studies such that they can be used in future QCA studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019131910.