Percutaneous cryoablation is a potentially curative treatment for hepatocellular carcinoma (HCC). After liver cryosurgery, rapid elevations of transaminases and bilirubin are common and usually transient that will normalize within a few days.This study retrospectively reviewed clinical data from65patients who underwent liver cryoablation in our hospital during the past4.5years. There are two groups, Group A consists of51patients who underwent cryoablation of HCC (long diameter less7cm), whilst Group B consists of14patients who underwent cryoablation of huge HCC (long diameter>7cm).In Group A, sixty-six percutaneous cryoablations were performed in these patients and transaminase and bilirubin levels before and after the procedure were observed. Although most patients received liver-protective treatment before cryosurgery, transaminase levels were double (mean alanine transaminase (ALT) and aspartate transaminase (AST) were71U/L and85U/L, respectively) the normal ranges in our hospital. One day after cryosurgery, ALT and AST had increased3.3-fold (peak mean was241U/L) and5-fold (peak mean was427U/L), respectively, but were close to the preoperative level5days post-cryosurgery. No significant increase of serum bilirubin was observed. Serum transaminase and bilirubin levels were compared between hepatitis B positive and hepatitis B negative patients. Only in the hepatitis B positive group were total bilirubin (74μmol/L/23μmol/L=3.2) and direct bilirubin (45μmol/L/12μmol/L=3.8) more than three times the preoperative level7-9days after treatment. Overall, ALT and AST are valuable as indicators of liver function impairment following cryosurgery. In patients with hepatitis B virus, serum bilirubin was three times the preoperative level7-9days after cryosurgery. Liver-protective treatment may alleviate liver function impairment due to cryosurgery.In Group B, all the patients survived cryosurgery and none died before leaving hospital two weeks later. Despite liver-protective treatment before cryosurgery, alanine transaminase (ALT) and aspartate transaminase (AST) levels were slightly higher than normal;1-2days after cryosurgery, they both increased significantly (means of196U/L and313U/L, respectively), but returned to preoperative levels two weeks post-cryosurgery. Before cryosurgery, mean total bilirubin (T.BIL) and direct bilirubin (D.BIL) levels were normal;8-10days after cryosurgery, they increased more than two-fold (means of39U/L and24μmnol/L, respectively), but returned to the preoperative level two weeks post-cryosurgery. Serum transaminase and bilirubin levels were compared between hepatitis B positive and negative patients. The hepatitis B negative group’s AST level increased significantly one day post-cryosurgery (mean,186U/L) and decreased to the preoperative level at day14. In the hepatitis B positive group, means transaminase (ALT,293U/L at day2; ALT,408U/L at day1) and bilirubin (T.BIL,57μmol/L at day10; D.BIL,36μmol/L at day8) reached peak values at different days post-cryosurgery. Overall, ALT and AST are valuable indicators of liver function impairment following cryosurgery. In patients with hepatitis B virus, close attention to the serum bilirubin level should be paid8-10days after cryosurgery. Liver-protective treatment may alleviate liver function impairment caused by cryosurgery of huge HCC.