With the proposal and implementation of the “Belt and Road” initiative, economic development requires the drive of a large number of talents and real industries. Local governments along the route also encourage universities and enterprises to carry out high-level school-enterprise cooperation to promote the effective sharing of education and economy, thus ensuring the development of the regional economy. In order to better adapt to relevant national policies, promote regional economic development, and supply high-quality and skilled talents to society, higher vocational colleges should strengthen education reform, introduce the school-enterprise cooperation mechanism, achieve the deep integration between schools and enterprises, and promote regional economic development. Based on this, this paper analyzes and studies the deep cooperation model between higher vocational colleges and enterprises under the “Belt and Road” initiative for reference.