Aim: Genetic susceptibility has been identified in idiosyncratic drug-induced liver injury, a potentially severe adverse reaction towards drugs, herbal products and dietary supplements. Drug-induced liver injury epigenetic signatures could help explain genetic regulatory mechanisms behind this disease and might provide disease biomarkers. This systematic review aims to analyse all available information on epigenetic risk association studies, as well as to include additional information on receiver operating characteristic analyses in idiosyncratic drug-induced liver injury when present. Methods: The main inclusion criteria were population studies on idiosyncratic drug-induced liver injury with significant risk association between drug-induced liver injury and an epigenetic regulation mechanism. Results: Out of the seven included articles six were focused on DNA methylation and one on long non-coding RNA. All of the studies were on drug-induced liver injury due to anti-tuberculosis drugs and came from Asia. CpG site methylation in the CYP2D6 (Odds ratio:9.19, 95% confidence interval:3.62-25.89, p-value:0.001) and NAT2 (Odds ratio:8.37, 95% confidence interval:2.39-29.32, p-value:0.001) promoters conferred the highest risk. Regarding the potential of epigenetic signatures as biomarkers, LINE-1 and ALU transposable elements hypomethylation levels showed an area under the curve value of 0.94, indicating their potential as biomarkers. Conclusions: The majority of the studies were on DNA methylation and hepatotoxicity due to anti-tuberculosis drugs, with all of them coming from Asia where tuberculosis is a public health burden. While this is an area that requires further research, the results of this systematic analysis suggest the potential of epigenetic regulation as a new diagnostic and therapeutic target.