The article addresses the approaches to measuring and assessing the limited and specific resource for the economy – human capital – in terms of information support for the quality of life management in the regions where “Yenisei Siberia” integrated investment project is being implemented (hereinafter – “Yenisei Siberia”), given the settlement system features and its professional structure, the current level of economic development and trends in production and demography, as well as the impact of ethnocultural, natural and geographical factors. The quality of life here is considered both as a statistically measurable quantity and as an estimated, subjective category determined by human behavior. It is the peoples’ well-being, based on the quality of life interpretation in the region that supports the human capital formation and its investment behavior, as well as the basis for cutting spatial inequality in the regions through coordination and joint management of the socio-economic spatial development. Taking into account such asymmetry in the socio-economic and socio-cultural situation in the regions, the authors propose an approach to the formation of homogeneous regional clusters for measuring the level of human capital and QOL in the territories of the macro-region of the Yenisei Siberia