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Start-ups are built by the charismatic leaders with innovative ideas, creativity, and distinguished expertise. However, they face huge challenges for growth and survival in an uncertain and competitive business eco-system. The aim of the present study is to examine the effect of entrepreneurial orientations with social media mediation on digital start-up sustainability. To conduct this research, active start-ups at the science and technology park of Tehran, Shiraz and Yazd universities have been identified in 2021. A 25-item questionnaire was used to collect data from 195 digital start-up managers. Data analysis has been done using SmartPLS3 software. The findings indicate that an innovative atmosphere, knowledge sharing and efficient communications have positive effects on the sustainability of digital startups, and the social media plays role as mediator. The results showed that social media contributes to increasing participation of employees in decision making process. Social media helps employees to share their knowledge, and establishes better interactions with the customers and stakeholders. As a result of better interaction, the company can respond to business challenges faster and operate in a more stable environment. Therefore, in today's turbulent market, attention to sustainability to achieve economic growth and development has been the focus of knowledge-based companies. [ABSTRACT FROM AUTHOR]