In the field of higher education, knowledge management has been considered as an important factor in achieving competitive advantages, improving the performance of universities and optimal use of intellectual capital. Universities are now the main generators of social and technological innovation. This, in turn, affects how universities manage human and technical resources strategically in search of competitive advantages, and on the other hand, the higher education sector faces significant competition worldwide. The aim of the present study was to investigate the mediating role of organizational innovation in the impact of strategic human resource management and knowledge management on competitive advantage, seeking to strengthen sustainable competitive advantage and organizational innovation in the higher education in non-profit universities of Mashhad. The current research was practical and descriptive and correlational in which the structural equation modeling method was used. The statistical population in this research was faculty members and senior managers in non-profit universities of Mashhad, whose number was 190, and according to Morgan's table, 123 people were selected as the sample size. The data collection tool is questionnaire (Kisingo et al., 2016). In order to determine the validity of the instrument, face validity, divergent validity, and convergent validity and construct validity of the instruments were examined and evaluated. All Cronbach's alpha values are higher than 0.7, which was in a good range of reliability. Hypotheses were tested using structural equation modeling and SMART-PLS software. The finding showed that the organizational innovation, Strategic Human Resource Managemen and knowledge management was significant impact on competitive advantage. The mediating role of organizational innovation in the relationship between Strategic Human Resource Management on sustainable competitive advantage and knowledge management on sustainable competitive advantages has been significant