INTRODUCTION: According to World Health Organisation, prevention and control of infection is a strategy designed to protect both patients and health care workers from infections. Lack of such strategy among health care workers has negative impact such as long-term hospitalization, death, and morbidity. Therefore, the aim of this study was to determine the practices of health care workers on prevention and control of infection at Keetmanshoop district Hospital. METHOD: A descriptive correlational cross-sectional study design was employed. Structured questionnaire was used to collect data from participants. Data collected were analysed using SPSS version 27. Multiple regression analysis was used to determine, the factors influencing the practices of health care workers on prevention and control of infection. RESULTS: The findings shows that more than 50% of the health care workers in Keetmanshoop district hospital have poor adherence to IPC. However, factors such as demographic characteristics and resources availability do not have any significance influence on the practices of prevention and control of infection. Significance contributing factors effect such as access of IPC resources (β = 0.31), individual health worker practices on IPC (β = 0.31) and practices of IPC at the facility (β = 76). Practices of hand hygiene was found at (β = -0.45) which is the negative effect on adherence. CONCLUSION: Therefore, this study concluded that hand hygiene; access of IPC resource and individual practices on prevention and control of infection were the main factors influence poor adherence on IPC at Keetmanshoop hospital.