Liver-derived paraoxonase-1 (PON1) enzyme that is found in the circulation is bound to high-density lipoproteins and reduces the amount of oxidized lipids with its antioxidant effect. Humans have at least three different PON gene regions which are adjacent to the other on the 7th chromosome. It has been shown that PON1 gene and its polymorphisms are related with various diseases. It is also known that, hepatitis C virus (HCV) is tightly associated with the cell lipoproteins in each step of its replication cycle leading to modulation of the host lipid metabolism. The aim of this study was to investigate the relationship between the response to chronic hepatitis C (CHC) therapy and aminoacid changes in 55' and 192' regions of PON1 enzyme believed to be involved in the pathophysiology of many chronic diseases. A total of 49 CHC patients (27 male, 22 female; mean age: 52.9 ± 12.6 yrs), all infected with HCV genotype 1b and positive for anti-HCV and HCV-RNA were included in the study. Patients who were HCV-RNA negative at the sixth month following at least once pegilated interferon + ribavirin treatment, were considered as therapy-responders, whereas those who were HCV-RNA positive were considered as non-responders. The genomic DNAs were isolated from patients' blood samples in their routine follow-ups and Q/R192 and L/M55 PON1 polymorphism analysis in 55. and 192. regions was performed by T-ARMS-PCR (Tetra-primer amplification refractory mutation system-polymerase chain reaction) method. In our study, the analysis of PON1 polymorphisms yielded 44.1% of LL, 44.1% of LM and 11.8% of MM genotypes at position 55 and 55.9% of QQ, 41.2% of QR, and 2.9% of RR genotypes at position 192 in therapy-responders. In the evaluation of combined genotype analysis of the patients, there was only one case who was responsive to treatment with LL/RR genotype. Of the patients, eight harbored LL/QQ genotypes and seven of them (87.5%) were responsive to treatment. However, statistical analysis indicated that there was no relationship between PON1 L/M55 and PON Q/R192 polymorphisms and response to CHC treatment (chi-square test, p> 0.05). Our data did not support a relationship between PON1 polymorphisms and response to CHC therapy, in contrast to a few studies pointing out of this correlation. This might be attributed to relatively low number of patients included. In conclusion, since antiviral agents used for CHC therapy are limited and costly, it was thought that further investigations with large numbers of patients should be conducted to establish the presence of any relationship between the response to CHC therapy and genotypes of the PON1 enzyme.