Objective: To study the protective effect in CCl4-induced liver injury by organoselenium from Se-enriched lactobacillus. Methods: (1) In the first series, forty-five animals were randomly divided into control (C) group, CCl4 group, CCl4 plus organoselenium group (CCl4-Se group). The liver injury was induced by abdominal injection of CCl4 every other day for 4 w. Changes of GSH-Px, CAT and SOD activities as well as MDA content in liver were estimated in the 2nd and 4th week after CCl4 injection respectively. (2) In the second series, forty-eight mice were randomly divided into C group, CCl4 group, CCl4 plus low dose organoselenium group (CCl4-LSe group) and CCl4 plus high dose organoselenium group (CCl4-HSe group). Changes of hepatocyte [Ca2+]i in animals in every group were investigated by means of confocal laser microscope on the 4th and 8th day after CCl4 injection respectively. Results: During the entire experimental period, liver MDA of CCl4 group was markedly superior to that of C and CCl4-Se groups, and the level of latter two groups was very close. The GSH-Px and CAT activities were higher in CCl4-Se group than in CCl4 group,but lower than that of C group. There were higher SOD activities in C and CCl4-Se groups compared to that in CCl4 group though without obvious difference. Average fluorescence pixels of hepatocyte [Ca2+]i in CCl4 group was 2.8 and 5.5 times higher than that of group C in the 4th and 8th day respectively,while those in CCl4-Se groups were significantly lower than those of CCl4 group, and close to C group. Conclusions: Organoselenium from Se-enriched lactobacillus, can protect hepatocyte [Ca2+]i homeostasis by reducing lipid peroxidation after CCl4 exposure.