Methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism was reported as a genetic variant in liver steatosis and fibrosis. This is a study of the association between MTHFR C677T polymorphism and HCV core with severity of steatosis in HCV GT4 patients. 111 HCV patients and 112 control subjects were recruited. Polymorphism was detected by RFLP analysis, core Ag was detected by ELISA. Combined HCV infection and MTHFR C677T polymorphism increases the risk to develop steatosis by 3.63- and 5.21-fold in subjects with single (CT) and double (TT) substitutions, respectively. Patients with chronic HCV infection had a 2.88- and 8.57-fold higher risk to develop steatosis in CT and TT genotypes, respectively, than patients with the (CC) genotype. No significant difference in core Ag titers were observed. MTHFR C677T polymorphism is a valuable genetic marker for steatosis, while HCV core Ag titer had no association with grades of steatosis in GT4 infections.