With the start of the military operation on the territory of Ukraine, anti-Russian sanctions have increased significantly. As early as February 24, 2022, the United States and its NATO allies announced new, stronger sanctions against Russia, its political leadership, oligarchs, and sectors of the economy. According to some estimates, almost half of the gold and foreign exchange (international) reserves were frozen. This deprived our country of many opportunities, including buying imported technologies, components, equipment and other goods for petrodollars. According to Washington, the new restrictions will more than halve Russian imports of high-tech products. The most active work on the implementation of programs and plans for import substitution them during the crises of 1998-1999, the global financial and economic crisis of 2008-2009, as well as in 2014-2016 after the introduction of anti-Russian sanctions. The authors showed that every time, as soon as the crises passed, and the price of oil and gas exports grew, the work on import substitution slowed down. In the context of tougher sanctions, the import of high-tech goods becomes almost impossible, so ministries and departments, state corporations, small and medium-sized businesses have again turned their attention to human capital, without the knowledge and competencies of which work on import substitution is impossible. The authors show the importance of human capital in the implementation of state import substitution programs under sanctions, emphasize the need for a real transition of the Russian economy from a raw-material to an innovative development path, and the introduction of a knowledge economy.