Abstract: Background　Osseointegration prostheses can directly transfer the load to the bone through the skin, which has certain advantages compared with traditional prosthetic sockets. However, they generally face the risk of infection caused by the unsealing of the soft tissue in the percutaneous part. Objective　To fabricate percutaneous prostheses via mechanical machining methods and apply distinct surface treatments to investigate their biological impacts, infection-resistant properties, and integration performance with soft tissues at transcutaneous interfaces. Methods　Thirty-six experimental percutaneous prostheses were prepared by machining and were randomly divided into groups A, B, C, D, E, and F, with 6 in each group. The surface of groups A and E were treated by sandblasting+ TiNbN coating, polishing+ TiNbN coating, high polishing, sandblasting+micro-arc oxidation, and acid etching, while the surface of group F was not treated. The effects of different percutaneous prosthesis extracts on MC3T3-E1 were analyzed using the MTT method. Eighteen New Zealand white rabbits were randomly divided into 6 groups, with 3 rabbits in each group. Two prostheses with the same surface treatment were implanted in the symmetrical part of the back of each experimental animal. The skin growth and recovery of the surgical site of the experimental animals were observed. At the same time, the white blood cell count, neutrophil count, platelet count, hemoglobin, alanine aminotransferase, creatinine, complement component 3, and complement component 4 were detected at different time points, and the effects of percutaneous prostheses with different surface treatments on hematological indexes of rabbits were analyzed. Finally, the liver, kidney tissue, and percutaneous materials were taken for histological examination. Results　The results of the MTT assay showed that there was no significant difference in cell survival rate between the experimental groups and the control group (P > 0.05). There was no significant difference in platelet count, hemoglobin, alanine aminotransferase, and creatinine in the same group at different time points after operation (P >0.05). On the 28th postoperative day, the WBC count in group B was lower than that in group F (P=0.019), and on the 42nd postoperative day, WBC counts in group A was lower than that in group F (P=0.002), groups B, C, D, E (P＜0.001). The level of complement component 3 in group B was lower than that in group F (P=0.039). On the 28th day after operation, the level of complement C4 in group B was lower than that in group A (P=0.009) and group E (P=0.006). There was no obvious degeneration, necrosis, or inflammatory changes in liver and kidney tissue sections. The histological examination of the percutaneous site showed that the percutaneous prosthesis treated with polishing and titanium-niobium-nitrogen coating was closely attached to the surrounding soft tissue. Conclusion　Percutaneous prostheses with different surface treatments demonstrates biosafety without causing significant tissue damage. Untreated surface prostheses exhibits lower infection resistance, while those subjected to polishing combined with TiNbN coating treatment shows enhanced antimicrobial efficacy and achieves more robust integration with surrounding soft tissues. This optimized surface modification protocol holds clinical potential as a transcutaneous interface processing technique for osseointegrated prostheses.