Clarifying the characteristics and influencing factors of specific soil enzyme activities in the process of vegetation restoration is of great significance to objectively revealing the change characteristics of microbial activity in the process of vegetation secondary succession. Based on the method of spatiotemporal interaction, this study selected five stages in the vegetation secondary succession process in the loess hilly region as the research objects, including farmland, grassland, shrubs, pioneer forests and top community stage, and discussed the change characteristics and influencing factors of specific soil enzyme activities of seven enzymes (β-1,4-glucose Glucosidase (BG), cellobio hydrolase (CBH), β-xylosidase (BX), N-acetyl-beta-D-glucosaminidase (NAG), leucine amino peptide (LAP), alaninase transaminase (ALT)) and alkaline phosphatase (AP)). The results showed that in the process of vegetation secondary succession, unit soil organic carbon (SOC), soil CBH, BX and NAG activities increased significantly at first and then decreased significantly (P < 0.05), and it reached the highest point in the pioneer forest stage; while the activities of three enzymes per unit soil microbial phospholipid fatty acid (PLFA) showed opposite trends (P < 0.05), and reached the highest level in the top community stage. Correlation analysis showed that soil CBH, BX and NAG enzyme activities per unit SOC and PLFA were significantly negatively correlated with soil pH and significantly positively correlated with soil DOC (P < 0.05); specific soil enzyme activity per unit SOC and PLFA were significantly positively correlated and negatively correlated with soil biological factors, respectively (P < 0.05). Redundancy analysis showed that the phosphorus content as well as the carbon and nitrogen content in the soil were the main driving factor for the change of specific enzyme activity per SOC and PLFA, respectively. This study provided new information for further revealing the soil nutrient cycling and quality changes during the secondary succession process.