Mallotus japonicus, belonging to Euphorbiaceae, has been known to possess various physiological activities such as anti-bacterial, anti-virus, and anti-inflammatory effects. This study was designed to investigate the anti-oxidative activity and anti-tumor effect of the Mallotus japonicus bark extracts with water and ethanol. The amount of total polyphenolic compounds was measured using gallic acid as a standard material. The ethanol extract showed higher contents (143.6±1.57 mg GAE/g) than the water extract (120.4±6.11 mg GAE/g). Based on this result, a modified DPPH assay was conducted for the free radical scavenging activities of water and ethanol extracts. The ethanol extract revealed 80% free radical scavenging activity, compared with the 60% activity of water extract. To identify the qualitative and quantitative analyses of ethanol extract, LC/MS/MS method was applied to 15 standard materials. The result showed the highest contents of bergenin and the existence of other materials except resveratrol and oxyresveratrol. Cytotoxicity test was performed with MTT assay. Whereas the ethanol extract showed no cytotoxicity to 293T of a normal cell, the effects of ethanol extract on Fadu cell (head and neck carcinoma cells) appeared to be toxic in a 125-250 μg/mL range of concentrations. These results imply the value of developing anti-oxidant and anti-tumor agents using the ethanol extract of Mallotus japonicus bark.