PurposeThere is increasing interest in the connection between Industry 4.0 (I4.0) and operational excellence approaches; however, studies on the integration between Six Sigma (SS) and I4.0 have been absent from the literature. Integration with I4.0 technologies can maximize the positive effects of SS. The purpose of this study is to understand what types of relationships exist between SS and I4.0 and with I4.0's technologies, as well as the benefits derived from this integration and future directions for this field of study.Design/methodology/approachA Systematic Literature Review (SLR) was carried out to analyze studies about connections between I4.0 technologies and SS. SLR analyzed 59 articles from 2013 to 2021 extracted from the Web of Science and Scopus databases, including documents from journals and conferences.FindingsThe SLR identified relationships between SS and several I4.0 technologies, the most cited and with the greatest possibilities of relationships being Big Data/Big Data Analytics (BDA) and Internet of Things (IoT). Three main types of relationships were identified: (1) support of I4.0 technologies to SS; (2) assistance from the SS to the introduction of I4.0 technologies, and, to a lesser extent; (3) incompatibilities between SS and I4.0 technologies. The benefits are mainly related to availability of large data sets and real-time information, enabling better decision-making in less time.Practical implicationsIn addition, the study can help managers to understand the integration relationships, which may encourage companies to adopt SS/Lean Six Sigma (LSS) in conjunction with I4.0 technologies. The results also drew attention to the incompatibilities between SS and I4.0 to anticipate potential barriers to implementation.Originality/valueThe study focuses on three previously unexplored subjects: the connection between SS and I4.0, the existing relationships with different technologies and the benefits resulting from the relationships. In addition, the study compiled and structured different types of relationships for SS and I4.0 and I4.0's technologies, identifying patterns and presenting evidence on how these relationships occur. Finally, exposes current trends and possible research directions.