Surgical Site Infection (SSI) is a one of the most common healthcare-associated infection which has a great impact on patient safety. Knowledge and practices of nurses play a key role for the prevention of spread of infection. To provide quality of care, it is very important for nurses to have good knowledge and practice towards prevention of SSI. A descriptive correlation study was conducted in two public hospitals Mayo Hospital and Lady Willingdon Hospital Lahore Pakistan to assess nurses’ knowledge and practice regarding prevention of Surgical Site Infection and to determine relationship between both variables. A validated questionnaire and convenient sampling technique was used on 131 nurses to collect data. Descriptive statistics and Pearson Product Moment Correlation test was used to analyze the data on SPSS version 21. Data revealed that majority of the participants were within age between 20-30 yrs with job experience 1-5 years, majority were holding General nursing and Midwifery Diploma. Majority nurses showed poor level of knowledge while good level of practices towards prevention of surgical site infection was found. A strong negative significant relationship was found between knowledge and practice of nurses. The Findings of current study demonstrated poor knowledge which suggests an urgent need of educational and awareness programs for improvement in nurses’ knowledge regarding prevention of surgical site infection.