Relevance of work is caused by the fact that now the integrated approach to system of professional orientation work with youth starting with the entrant becomes one of important tasks for higher education institutions and finishing the graduate taking into account their personal opportunities and abilities, and also a state and prospects of development of regional economy and labor market. In article functions of the main subjects on career guidance of youth in general are considered and the emphasis for a role of higher education institutions in this direction is placed. Results of research of preferences of entrants are given in the choice of educational services, an assessment of efficiency of professional orientation work in the region, conclusions are drawn. Need of development of the Concept of professional orientation work of higher educational institutions of the Orenburg region with youth is proved. The principles are formulated, the mechanism of realization of professional orientation work is presented and the main directions of improvement of work of higher education institutions of the Orenburg region on career guidance stages are defined.