Aims: This systematic review aimed to evaluate whether calcium silicate-based sealers are less cytotoxicity and genotoxicity than epoxy resin-based sealers.
 Materials and Methods: Systematic searches were conducted for studies published up to September 27th, 2022, without restriction for language or year of publication, in the following databases: MEDLINE/PubMed, Scopus, Web of Science and Grey Literature Report. Only in vitro studies that evaluated the cytotoxicity or genotoxicity of calcium silicate and epoxy resin-based sealers were included. The quality assessment was performed.
 Results: After duplicate removal and eligibility criteria assessment, a total of thirty-four studies were included. Twenty-eight studies had a low risk of bias, and six studies had a moderate risk of bias. In general, calcium silicate-based sealers had a lower cytotoxic and genotoxic potential than epoxy-resin based sealers.
 Conclusions: Based on the findings from in vitro studies, calcium silicate-based sealers are less cytotoxic and genotoxic than epoxy resin-based sealers.