The present study determined some critical information about the distribution of HCV genotypes in Jazan, Saudi Arabia. Genotyping analysis was performed in 198 HCV-RNA positive patients. The HCV genotypes frequency was determined as follows: genotype 1a in 36 (18.1%) patients, genotype 1b in 27 (13.6%), genotype 2 in 6 (3.0%) patients, 3 in 9 (4.5%), and mixed infection in 9 (4.5%) patients. Of 8 mixed genotype infection patients, mixed inter-genotype infection 1 and 4 was the most common (56.0 %). Their ages range between (23 and 55) years.