The Hyalomma ticks are hematophagous arthropods that can transmit a wide range of pathogens. Recently, the proliferation of Hyalomma ticks in Kalamaili Nature Reserve (KNR), Xinjiang, has increasingly endangered the local wildlife and the reserve's staff. During the 2021 and 2022, this research delineated a 25km² study area within the core zone of the reserve to examine the spatial distribution and influencing factors of Hyalomma ticks. It particularly concentrated on elucidating the spatial interactions among the Hyalomma ticks, Przewalski's horses, and rodent species. The study employed semi-variance analysis to assess the spatial correlation of Hyalomma ticks' distribution. Bivariate spatial autocorrelation methods were used to evaluate the spatial clustering degree of Hyalomma ticks with respect to their host animals. Additionally, a structural equation model was applied to delineate the relationship between the abundance of Hyalomma ticks and various environmental factors. The results are as follows: 1) The block kurtosis ratio in the semi-variance for Hyalomma ticks is above 0.75, indicating a low spatial autocorrelation and suggesting that the distribution of Hyalomma ticks is more influenced by host and environmental factors. 2) The bivariate local indicators spatial autocorrelation (LISA) clustering diagram demonstrates a more pronounced spatial clustering relationship between Hyalomma ticks and Przewalski's horses compared to that between Hyalomma ticks and rodents. 3) The multivariate mixed structural equation model shows a relatively good fit (R²=0.70), indicating that climate, vegetation, and host variables significantly influence the abundance of the Hyalomma ticks. In conclusion, the study found that the primary factor influencing the distribution of Hyalomma ticks in the core area of the KNR was the host, with a stronger spatial clustering relationship observed between Przewalski's horses and Hyalomma ticks compared to rodents. The expansion of Hyalomma ticks alongside larger host species poses a direct threat to coexisting wildlife, particularly within the core zone. The reintroduction of wildlife can potentially have indirect effects on other species within the ecological chain. With the reintroduction of Przewalski's horses, there have been changes in the distribution of parasites in the area, likely due to the parasites adapting to new environmental conditions, and this adaptability is dependent on the distribution of Przewalski's horses. This phenomenon highlights the interconnectedness of various components within an ecosystem, where changes in the ecological chain can potentially lead to adaptations in other organisms. This issue underscores the importance of conducting monitoring efforts for the reintroduction of the endangered wildlife, and the research findings expand our perspectives on the control and management of tick-borne diseases in wildlife.