We aimed to determine the relationships between iron overload and HFE gene mutation in chronic liver disease in Turkey. One hundred thirteen chronic liver disease patients and 138 healthy controls were evaluated regarding their clinical, biochemical, and genetic parameters. Each group was divided into two subgroups according to transferrin saturation (TS) (45% and > 45%). HFE gene mutation was analyzed by the PCR-RFLP method. C282Y homozygote, heterozygote, and wild-type mutation rates were 1.7%, 0%, and 98.3% in patients and 0%, 1.4%, and 98.6% in controls, respectively. H63D homozygote, heterozygote, and wild-type mutation rates were 1.8%, 24.7%, and 73.5% in patients and 1.4%, 24%, and 74.6% in controls, respectively. Mutation rates were not statistically different in patients with high and normal TS. Iron overload was positively correlated with biochemical activity and Child-Pugh score (P < 0.05). In multivariate analysis, H63D homozygotic mutation was an independent factor for the development of hepatocellular carcinoma (P = 0.004). We conclude that C282Y mutation is very rare in Turkey. Iron overload is not related to H63D mutation but is positively correlated with biochemical activity and Child-Pugh score in chronic liver diseases.