The study of regional population evolution is helpful to reveal the rule of population distribution and is important for reasonably making population development policy, and for the promotion of regional sustainable development. By using population structure indexes, spatial auto-correlation analysis and GIS technology, the spatio-temporal dynamics of population distribution in the middle and southern Liaoning urban agglomeration have been analyzed since the 1990s. The results show that: (1) the population quantity of different cities in the middle and southern Liaoning urban agglomeration is quite different, with the density being higher in the west, and the distribution concentrated along traffic axes, and the population distribution of different cities presents distinct positive correlation in 2007. (2) Since the 1990s, there are many differences among the population amplitudes in different cities. The population distribution is of concentration pattern, and the population centralization is enhanced. From 1993 to 2007, the center of gravity moves from northeast to southwest. This paper shows that statistic analysis of spatial auto-correlation should be a good method to explore the hotspots and inner mechanism of distribution, centralization and change of population．