Under the Belt and Road, China's OFDI has shaped their industrial structure upgrading in Mekong river nations. This paper analyzes its impacting mechanism, establishes national industrial structure upgrading model, and uses direct investment stock and economic indicators of China on five Mekong river nations to analyze its impacts of China's OFDI on Mekong river nations in their industrial structure upgrading via medium effect. China's OFDI pushes their industrial structure upgrading generally, with an annual increasing rate 7.31 units during 2008 to 2018, through technical overflow, productive elements supply and three productivity effects, of which productivity effect contributes the most. Under the background of Lancangjiang-Mekong cooperation, it should be addressed that China's OFDI exerts a positive influence on Mekong river nations. A supportive investment policy will better construct the united Lancangjiang-Mekong coalition.