This paper researches the parameters which can influence the development of small and medium-sized business in the regions of the Russian Federation. The theme is relevant because of the Russian government's special attitude to the small and medium-sized entrepreneurship (SME). Nowadays the national project “Small and Medium-Sized Business and Support for Individual Entrepreneurs” takes place, but its result might depend on some features of the regions. The main goal of the research is to find some factors that influence a share of the gross regional product produced by SMEs. For our research the sample includes data of 85 regions of the RF at the end of 2021. After the tests and changes needed, we estimated an econometric equation using OLS method. The independent variables in the model are as follows: a share of urban population which determines the basic conditions for a business, a number of the universities as a characteristic of the opportunities for mastering some professional skills, a wages index and an informal sector employment share, the amount of investment in fixed assets as a level of the regional development, indexes of innovation of a regional economy and SMEs, loans to SMEs, a number of the government's programs to the SMEs support. Statistics were taken from the Federal State Statistics Service publications, information-analytical materials of the Bank of Russia and other sources. The hypothesis of the research is our assumption of the positive influence of the factors under investigation on the dependent variable. The hypothesis was proved partly because not all the factors influence the development of SMEs.