The article presents the results of the empirical study of the value and meaning-of-life orientations of Russian entrepreneurs as factors of their economic self-determination. The object of the study was entrepreneurs of various spheres of small and medium-sized businesses living and doing business in Moscow and other regions of Central Russia (Vladimir, Kostroma and Yaroslavl) – a total of 120 people (i.e. 60 respondents in each sample). To diagnose the features of the value-semantic sphere of the personality of entrepreneurs, the following methods were used: the methodology «Questionnaire of values of Sh. Schwartz» in the adaptation of V. N. Karandashev and the Test «Life Orientations» by D. A. Leontiev. As meaningful characteristics of economic self-determination, the following were identified and analyzed: the level of business activity and its dynamics (according to the respondent's selfassessment) and psychological attitudes to entrepreneurship: assessments of the favorable economic conditions and their own capabilities in increasing the success of their business, assessments of the success of their entrepreneurial activity and satisfaction with its results. The results of the regression analysis showed that the assessments of the level of respondents' business activity and the dynamics of its change are statistically determined by the severity of the meaning-of-life orientation «Process of life» and the value orientation «Stimulation». The assessment of one's own capabilities in achieving the success of one's entrepreneurial activity is statistically determined by the severity of the meaning of life orientation – the «Locus of Self» and the high significance of the value of «Hedonism». The assessment of the success of one's entrepreneurial activity and satisfaction with its economic results depends on such a meaningful life orientation as the «Locus of life» and values – «Stimulation». Thus, the more an entrepreneur is satisfied with his life in the present, the more he perceives the process of his life as interesting, emotionally saturated and filled with meaning, the higher the entrepreneur's conviction in his ability to control his life, freedom in decision-making and their implementation, along with the desire for novelty and experiences, the more highly he appreciates the level of his business activity and the dynamics of its changes, the success of his entrepreneurial activity and satisfaction with its economic results. The results of the study confirm the validity of considering the meaning of life and value orientations of the individual as factors of economic self-determination of entrepreneurs.