On one hand, habitat quality has become a main factor to measure regionally ecological health and sustainable state. On the other hand, the ecological quality and degradation process in Guangdong Province are complex though solid researches were rarely recorded. Therefore, this paper used the FLUS-InVEST coupling model to study the habitat quality changes in Guangdong Province from 1980 to 2020 and forecasted the future trends from 2020 to 2035. The main results are as follows:(1) Forest land and cultivated land were the main land uses in Guangdong Province, which constituted the landscape matrix of land cover. Construction land has increased rapidly, with the area of 1.2 times in the past 40 years. The area of cultivated land has dropped sharply, with the ratio decreased from 27.1% to 22.8%. The area of construction land was expected to increase and the area of cultivated land would decrease to less than 22% in the next 15 years if following the trends. (2) Forest land was mainly in the northern ecological development area. The cultivated land was concentrated in the east and west wings of Guangdong Province. Except for several large reservoir spots, wetland distributed throughout the study area. The forest land in the northern ecological development area has shown the characteristics of fragmentation, and the cultivated land and wetland in some areas had a trend of decreasing and fragmentation. (3) In the past 40 years, the area of improved habitat quality accounted for the largest proportion (44%), followed by areas that remained unchanged (29%) and decreased (27%). Approximate 79% of regional habitat quality indices increased or decreased between -0.1 and 0.1. In the next 15 years, the proportion of area where habitat quality continued to increase will decrease to 39%. The proportion will increase to 31%, and the low-level habitat patches in the core area of the Pearl River Delta were expanding. (4) Without land-use changes, there were still diverse habitat-quality changes in some areas. But habitat-quality changes were greater in areas where land uses have been transferred from one to another. The results concluded that the habitat quality in Guangdong Province had the characteristics of overall good advantages and prominent local deterioration, which was the regional characteristics that needed to be recognized in the present ecological restoration work. Relationship between land-use change and habitat-quality effect were much more complex, which needed further reveal in the future studies.