Objective To analyze the effect of triamcinolone acetonide local block therapy in the treatment of keloids. Methods A total of 80 patients with keloids admitted to Huaihe Hospital of Henan University from January to December 2024 were selected, and they were divided into the control group and the observation group by the random number table method, with 40 patients in each group. The control group received prednisolone local block therapy, and the observation group received triamcinolone acetonide local block therapy. The treatment effect, scar hyperplasia-related factor and skin status were compared between the two groups. Results The total effective rate of the observation group (92.50%) was higher than that of the control group (75.00%) (P<0.05). The levels of VEGF, EGF and TGF-β1 in the two groups after treatment were lower than those before treatment, and those in the observation group were lower than those in the control group (P<0.05). The scar area, pigment content, and moisture content in the two groups after treatment were better than those before treatment, and those in the observation group were better than those in the control group (P<0.05). There was no significant difference in oil content between the two groups (P>0.05). Conclusion The application of triamcinolone acetonide local block therapy in the treatment of patients with keloids has a good effect. It can actively regulate the levels of internal scar hyperplasia-related factors, improve the patient's skin status, and reduce the scar area, which is worthy of clinical application.