Abstract: Balanced economic development is an important connotation for measuring the high-quality development of regional economies, which is also a requirement for the development of the new normal in low economic development provinces such as Guizhou. This paper constructed the county economic density evaluation index system for 2000, 2010 and 2020. The entropy weight TOPSIS method, kernel density estimation method, spatial autocorrelation method and spatial panel model were applied to measure the comprehensive score of economic density. The spatio-temporal characteristics and influencing factors were also explored. The results showed that: (1) the economic density of Guizhou's counties generally increased over time. The nuclear density curve was dominated by multiple peaks, with the main peak increasing over time and a small contraction in width from 2000-2020. (2) Spatially, the centers of high economic density were shrinking, with positive growth counties dominating in 2000-2010 and negative growth counties dominating in 2010-2020; In the global spatial autocorrelation, the degree of spatial agglomeration of economic density increased and then decreased. The local spatial autocorrelation was dominated by the agglomeration of the high-high and the low-low modes. (3) There was a significant spatially endogenous interaction of economic density, where each 1% increase in economic density in the neighboring counties would promote a 0.2% increase in local economic density. (4) Regarding the affecting factors, talent endowment and medical beds had a positive effect on economic density, and other factors had a negative effect. The strength of the direct effect is ranked as follows: talent endowment > precipitation #> population aging #> ethnic structure #> vegetation cover #> medical beds (# indicates a negative effect). The size of spatial spillover effect contribution was ranked as follows: talent endowment > population aging #> precipitation #> ethnic structure #> medical beds. Therefore, Guizhou should focus on the regional balance of economic development, and make up for the shortcomings of economic development in ethnic counties while continuing to attract talents and improve social welfare conditions.