The purpose of this research is to investigate and analyze the practices related to Human Resource Management in Startup companies in the Regional Unit of Larissa. As part of the study, a survey was conducted on a sample of start-ups. Regarding the structure of the research, first of all, reference is made to the definition of human resources management, its objectives and the activities it includes. Next, the start-up is studied, its development, the challenges it is called to face throughout its existence. At the second level, the contribution of universities and innovation centers to the promotion of entrepreneurship and innovation is analyzed. Next, the extent to which, the Startup companies of the Regional Unit of Larissa use certain methods of attracting employees, is investigated. In addition, the degree of utilization of various selection methods, training and development, communication, retention of human resources and methods of remuneration and benefits are examined. Finally, the change in the total number of staff in the surveyed companies is studied, as well as the employment arrangements that are applied in each company. Actually, a quantitative survey was conducted with a questionnaire of a specific structure. In conclusion, through the quantitative research and the analysis of its results, an attempt was made to record the practices applied by the companies and concerning their human resources. The questionnaire was distributed to specific companies in Larissa that managed to prevail in the market immediately, attracting a large audience either in the local market or worldwide.