[Objective] The impact of human activity intensity on habitat quality in nature reserves was analyzed in order to provide a basis for improving habitat quality and spatial optimization in nature reserves. [Methods] Based on 2021 land use data and other spatial data, the main land use conflict problems occurring in the He’nan Yellow River wetland national nature reserve, the spatial distribution characteristics of habitat quality, and human activity impacts and their spatial correlations were analyzed using the InVEST model, the human impact index model, and the bivariate spatial autocorrelation model. [Results] ① The main land conflict types in the study areas were rural construction land, farmland, and fish ponds, accounting for 28.85% of the total area. ② The human influence index was above the intermediate level, accounting for 37.97% of the total area; the human influence index was high in the east and west, and low in the middle area. ③ The mean value of the habitat quality index was 0.65, and the area below the medium habitat quality level accounted for 52.46% of the total area, which was generally below the medium level. ④ There was a negative spatial correlation between the human impact index and habitat quality (the Moran’s I was -0.519). [Conclusion] With future integration and optimization, the Yellow River wetland national nature reserve will need to remove farmland and fish ponds, focus protection efforts on river wetlands in the eastern plains, optimize the zone of protection, and develop corresponding control and optimization strategies based on the characteristics of human activities to improve habitat quality.