Arsenic is a metalloid and a well known carcinogen. Chronic exposure to arsenic in drinking water induces oxidative damage to the liver. It is also associated with irrevocable pathological lesions in the liver. In the current study, HepG2 cells were used as a model to understand the cytotoxicity of arsenate and the effect of a standardized extract of Ixora coccinea flowers on arsenic-induced liver injury. Reactive oxygen species (ROS), mitochondrial membrane potential (MMP), DNA damage and percentage apoptosis were evaluated in HepG2 cells to understand the cytotoxicity. Ixora coccinea is a shrub widely used in Ayurveda and traditional medicinal practices in India and Asia. The flower extract was analysed for free radical scavenging ability using 2,2-diphenylpicrylhydrazyl (DPPH), 2,2`-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and nitric oxide scavenging assay. ROS, MMP and DNA damage were considered for assessing the cytoprotective effect of the extract against arsenate-induced cellular damage. IC₅₀ value obtained for the cell line was 46 μM. Cellular apoptosis was measured using fluorescent microscopy. Pretreatment of HepG2 cells with Ixora coccinea flower aqueous extract significantly (p < 0.01) attenuated the ROS levels, altered MMP, apoptosis and DNA damage. Our study demonstrated the role of Ixora coccinea flower extract in combating arsenic-induced toxicity in HepG2 cells.