The article considers the principles of the interaction of transnational entrepreneurship structures with start-ups in the conditions of the Fourth Industrial Revolution. The main tendencies of startup project functioning in conditions of uncertainty and risks are highlighted. It is noted that startup projects are one of the forms of implementing innovations and represents an important factor in strengthening the innovative component of the economy’s development. The need for new scientific approaches to determining the development strategy of startup projects in the conditions of Industry 4.0 is indicated. The factors of rapid growth and scaling up of a startup project are given. It is noted that due to the need to develop startups with significant resources and a network of customers, newly established enterprises do not have, in contrast to the powerful structures of the transnational type of business, the ideas of economical and lean production, implemented through the form of startup projects. It is emphasized that this type of startup promotes experimentation as an iterative process to reduce uncertainty, attract stakeholders and promote collective learning at relatively low cost. The advantages of cooperation between startup companies and multinational corporations were identified. It is noted that due to the need to develop startups with significant resources and a network of customers, newly established enterprises do not have, in contrast to the powerful structures of the transnational type of business, the ideas of lean production, implemented through the form of startup projects. It is emphasized that this type of startup promotes experimentation as an iterative process to reduce uncertainty, attract stakeholders and promote collective learning at relatively low cost. The advantages of cooperation between startup companies and multinational corporations were identified. It was noted that the speed of product scaling is increasing under the conditions of the Fourth Industrial Revolution, especially this statement is true for new products in the field of information and communication technologies. The main elements of the startup ecosystem in cooperation with a multinational company in the conditions of Industry 4.0 are given. The difference between newly created companies and startups is highlighted. Possibilities of cooperation between structures of transnational type and startup companies are considered on the example of Österreichische Mineralölverwaltung AG (OMV), an Austrian integrated oil and gas company with headquarters in Vienna. The key performance indicators of the multinational company OMV are presented, and it is stated that the digital transformation of the entire group of companies combines numerous initiatives for advanced analysis, cyber-security, process digitization, automation, communication in the development of elements of Industry 4.0.