Objective: The objective of this study is to determine the practice and associated factors of HPV vaccine among school girls in Melaka, Malaysia. Methodology: A total number of 612 secondary school girls participated in this study. The questionnaire consists of 38 questions which included 3 sections. The first section is about sociodemography. The Second section is about knowledge and awareness of HPV vaccines. The third section is about practices with associated barriers of HPV vaccination. Verbal consent was obtained from all participants, and data were analyzed using SPSS 13. Results: A total number of 612 secondary school girl students participated in this study. The mean age was 13.93±SD (1.09); minimum age was 13 years old and maximum was 17 years old. The majority of them was Malay, from rural areas and had a family monthly income of RM 3000 or less (91.8%, 53.1%, 69.6%; respectively). The majority of the parents of the school girls were with secondary education level (56.4%). The majority of the participants did not have a family history of cervical cancer (99.0%). The prevalence of HPV vaccination was 77.9% among school girls in Melaka. The majority of the participants were vaccinated in their schools (77.0%). About 69% knew about cervical cancer and 77.6% had ever heard about HPV vaccine. Regarding the factors that influence the practice of uptake HPV vaccine, they were age, race, income, parents' education, knowledge about cervical cancer, heard about HPV vaccine and place of getting the vaccine (p<0.001). Conclusion: The prevalence of HPV vaccine among school girls is high. Age, race, income, parents' education, knowledge about cervical cancer, heard about HPV vaccine and place of getting the vaccine were the significant factors that influence the practice of uptake HPV vaccine among school girls.