Needle stick injuries and other sharp injuries present a major risk for infection with hepatitis B virus, hepatitis C virus and HIV. The present Cross-sectional descriptive study was conducted with an aim to identify the level of knowledge regarding prevention of needle stick injuries among staff nurses working at NMCH, Nellore. 100 Subjects were selected by using Convenience sampling technique. Data was obtained by using pretested self-administered questionnaire. Confidentiality was maintained throughout the study. Data was analyzed by using descriptive and inferential statics. Chi-square test was applied as a test of significance with fixing the p-value of 0.05 as significant. Pertaining to the study results out of 100 staff nurses, 8 (8%) were had in adequate knowledge, 12 (12 %) were had moderately adequate knowledge and 80(80%) were had adequate knowledge regarding needle stick injuries. Hence the study concluded that Needle stick injury is the most important occupational health hazard in nurses with alarmingly high rates. Reporting to the concerned authorities, screening of nurses after needle stick injury and promotion of safety measures against it should be greatly encouraged.