Objective To investigate the expression level of CXCL16 and its clinical significance in the local tissue manifestations of aseptic loosening after total hip arthroplasty. Methods A total of 44 patients who underwent revision of aseptic prosthesis loosening from June 2017 to June 2023 were selected as the experimental group, and 44 patients who underwent primary total hip arthroplasty in our hospital during the same period were selected as the control group. HE staining was used to observe the morphological changes and immunohistochemistry was used to detect the expression of real CXCL16. Results HE staining results showed that there were more multinucleated giant cells infiltrated in the border membrane tissue of the prosthesis in the experimental group, while the histological scoring results showed that there was a significant difference between the histological scores of the two groups (P < 0.01). Immunohistochemical staining showed that the expression level of CXCL16 in the perimembranous tissues of patients in the experimental group was significantly higher than that in the control group (2 = 55.942, P < 0.01). The results of stratified analysis showed that there was statistical significance between histologic scores and different prosthesis types (P < 0.01), and between OD values of CXCL16 and different prosthesis types and prosthesis survival (P < 0.05). The results of correlation analysis showed that there was a correlation between histologic score and prosthesis survival (r = 0.383, P < 0.05), and there was a correlation between the expression level of CXCL16 and the OD value of CXCL16, prosthesis survival, and pre-revision Harris score (P < 0.05). Conclusion The expression level of CXCL16 in the prosthesis border membrane tissue of patients with aseptic loosening after artificial hip arthroplasty was significantly higher than that of the control group, and it is hypothesized that this factor is greatly likely to be involved in the pathogenesis of aseptic loosening.