Hepatitis C virus (HCV) is a widely spread disease all over the world. HCV has very high mutation rate that makes it resistant to antibodies. Modeling HCV to identify the virus mutation process is essential to its detection and predicting its evolution. This paper presents a model based framework for estimating mutation rate of HCV in two steps. Firstly profile hidden Markov model (PHMM) architecture was builder to select the sequences which represents sequence per year. Secondly mutation rate was calculated by using pair-wise distance method between sequences. A pilot study is conducted on NS5B zone of HCV dataset of genotype 4 subtype a (HCV4a) in Egypt.