Human trafficking is a serious crime and a multi-dimensional threat. It is treatment of human beings as private property andcommodity, which deprive them on the possibility of using their fundamental rights. The information requirements and methods of data collection of this research focused on examining legal and practical challenges for effective prevention of human trafficking in Amhara National Regional State (herein after, ANRS). It tried to identify gaps in policy, legislation and practicesthat affect effective prevention of human trafficking in ANRS.Accordingly, within qualitative approach, qualitative data collection method is used to this research.It focused on examining ANRSspecific court cases, General Attorney‟sofficial report and used limited number of informants to gather in-depthinformation.The studies conducted by researchers due to limitations of time and place now a day‟s their finding cannot reflect the current legal and practical gaps on prevention of human trafficking in Ethiopia in general and in ANRS in particular. They did not well address those legal and practical challenges on prevention of human trafficking in the region.Ethiopia is a major source of irregular migration in theintergovernmental authority for development (herein after, IGAD) region. In spite of a number of initiatives by the government and other stakeholders, irregular migration remains a challenge for the country.The Federal government has ratified a variety of international instruments that provide for protection of migrants and victims of trafficking. The proclamation for the prevention of human trafficking provides much harsher sanctions for the perpetrators of these crimes to pass proportional sentence against criminals.However, Ethiopia has not given priority at the policy level for prevention of trafficking of personsat the national level.It makes the ANRS government prevention mechanism not to be effective on prevention of human trafficking. Lack of special compensation procedure for victims and clarity on some provisions of the proclamation is also the legal challenge that affects effective prevention of human trafficking in ANRS