The present study was designed to detect the possible potential hepatoprotective effect of the aquatic blue-green alga Aphanizomenon flos-aquae (AFA) against hepatic intoxication induced by carbon tetrachloride (CCl₄) in adult male mice. A total of 28 Swiss adult albino mice (Mus musculus) of CD1 strain, were allotted to four groups, each group of seven mice. Group (I) negative control group: contains normal healthy mice; group (II) positive control group: are mice who received a dose of  CCl₄ (0.5 mg/kg body weight), dissolved in olive oil, through intraperitoneal injections twice a week for six weeks; group (III) AFA control group: received a daily oral dose of AFA (72.8 mg/kg body weight) for 10 consecutive days; group (IV): they are mice that were given a daily oral prophylactic dose of AFA (72.8 mg/kg body weight) for a period of  10 continuous days prior to treatment with CCl4. Carbon tetrachloride caused liver damage as evidenced by marked changes in the normal cellular structure of the hepatocytes such as swelling of the mitochondria, loss of glycogen rosettes, condensation of chromatin, and loss of definitive shape of the nucleus. However, the protection offered by Aphanizomenon flos-aquae suppressed significantly cellular damage caused by CCl₄; as indicated by the normal nucleus and nuclear chromatin distribution, increase in glycogen content, and normal mitochondrial structure. These results substantiated the potential hepatoprotective activity of AFA.