© 2020 Elsevier GmbHBackground: Boron is a prominent part of the human diet and one of the essential trace elements for humans. Dietary boron is mostly transformed into boric acid within the body and has been associated with desirable health outcomes. Non-dietary resources of boron, such as boron-based drugs and occupational exposure, might lead to excessive boron levels in the blood and provoke health adversities. The liver might be particularly sensitive to boron intake with ample evidence suggesting a relation between boron and liver function, although the underlying molecular processes remain largely unknown. Methods: In order to better understand boron-related metabolism and molecular mechanisms associated with a cytotoxic level of boric acid, the half-maximal inhibitory concentration (IC50) of boric acid for the hepatoma cell line (HepG2) was determined using the XTT assay. Cellular responses followed by boric acid treatment at this concentration were investigated using genotoxicity assays and microarray hybridizations. Enrichment analyses were carried out to find out over-represented biological processes using the list of differentially expressed genes identified within the gene expression analysis. Results: DNA breaks were detected in HepG2 cells treated with 24 mM boric acid, the estimated IC50-level of boric acid. On the other hand, pleiotropic transcriptomic effects, including cell cycle arrest, DNA repair, and apoptosis as well as altered expression of Phase I and Phase II enzymes, amino acid metabolism, and lipid metabolism were discerned in microarray analyses. Conclusion: HepG2 cells treated with a growth-inhibitory concentration of boric acid for 24 h exhibited a senescence-like transcriptomic profile along with DNA damage. Further studies might help in understanding the concentration-dependent effects and mechanisms of boric acid.