A molecular study was conducted to investigate the prevalence of Hepatitis C virus genotypes in HCV infected population of Jazan, Saudi Arabia. Samples were collected between February 2010 and March 2013 from all hepatitis C patients referred from peripheral hospitals to King Fahd Hospital. Of the 198 studied participants. 36(18.2%) of them were infected with 1a, 27(13.6%) with 1b, 6(3.0%) with 2 and 9(4.5%) with genotype 3 of hepatitis C. Mixed infection was found in 9 patients [1&4 in 9(4.5%).  The most prevalent genotype was 3a with rate of 50% followed by genotype 3b and 1a, respectively. Nine samples remained untyped, suggesting the need of further investigation of genotypes in this region. It has been proposed that sequencing of these samples may be helpful to unreveal these genotypes and further epidemiology of HCV genotypes. Furthermore, extensive and large scale studies are needed to understand the epidemiology of HCV genotypes, as no such study has been carried in this province. Qualitative analysis of these samples using PCR resulted in 28 positive samples. The PCR positive samples were subjected to genotyping using the method described by Ohno et al (J Clin Microbiol 35:201–202, 1997) with minor modifications. Genotyping of 28 samples revealed three different genotypes including 3a, 3b and 1a.  Significance and impact of the study: The present study determined some critical information about the distribution of HCV genotypes in Jazan, Saudi Arabia.