Background Non-suicidal self-injury (NSSI) is a self-destructive act that represents a considerable burden on the individual and society. Low self-esteem may be a psychological variable that is related to NSSI. However, little is known about the nature of this relationship in adulthood. This systematic review therefore aimed to provide a synthesis of the available literature on the relationship between self-esteem and NSSI. Methods Articles were independently identified and risk of bias assessed by two reviewers searching PsycINFO, CINAHL, Medline and Web of Science databases. Inclusion criteria were: (1) a mean sample age of eighteen years or over (2) full manuscripts available in English (3) assessment of NSSI (4) assessment(s) of self-esteem. A narrative synthesis of results was undertaken. A random-effects meta-analysis of differences in self-esteem between NSSI and non-NSSI groups was also undertaken. Results Seventeen studies were identified and indicated a significant negative relationship between self-esteem and NSSI. The meta-analysis indicated lower self-esteem in those with experiences of NSSI versus those without, d = 0.59 – 1.17. Results suggested that although low self-esteem and NSSI are related in both clinical and non-clinical populations, there are a number of factors which also influence this relationship. Limitations The absence of longitudinal research is a major limitation of this literature. Conclusions It will be important for clinicians to consider the impact of self-esteem in those seeking support for NSSI. Further research should undertake longitudinal research to better understand the self-esteem and NSSI relationship.