Objective To investigate the changes of serum alpha fetoprotein (AFP), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199) and carcinoembryonic antigen (CEA) in patients with chronic hepatitis B, liver cirrhosis and primary liver cancer, and their value in judging the degree of liver injury. Methods A total of 145 patients with chronic HBV infection (46 patients with chronic hepatitis B, 44 patients with cirrhosis and 55 patients with primary liver cancer) who were admitted to the hospital from June 2014 to December 2016 were selected as the subjects. At the same time, 60 healthy volunteers were selected as the control group. The serum AFP, CA125, CA199 and CEA levels were detected by electrochemiluminescence. Results Serum AFP levels in the liver cancer group, liver cirrhosis group, chronic hepatitis group and control group were (60.34±10.68) ng/ml, (5.86±2.68) ng/ml, (4.46±1.64) ng/ml and (2.63±1.12) ng/ml, respectively while CEA levels were (2.62±2.11) ng/ml, (1.98±2.39) ng/ml, (1.49±2.13) ng/ ml and (1.84±1.21) ng/ml, respectively. Serum AFP and CEA levels in the liver cancer group were significantly higher than those in the other three groups (P < 0.05), and levels of AFP and CEA increased gradually with the development of the disease (P<0.05). The CA125 levels in the liver cancer group, liver cirrhosis group, chronic hepatitis group and control group were (16.32±4.84) U/ml, (24.58±6.03) U/ml, (11.34±3.12) U/ml and (14.26±2.69) U/ml, respectively, and the CA125 level in the liver cirrhosis group was significantly higher than that in the other three groups (P<0.05). There was no significant difference in the CA199 level among the four groups (P>0.05). Conclusion The serum CA125 level is positively correlated with the severity of hepatitis B, and it increases gradually with the amount of ascites. Therefore, CA125 is of great value in monitoring changes of ascites and judging the prognosis. Serum AFP and CEA may increase slightly with the progression of liver disease, and they are of certain monitoring value for early liver cancer