Abstract Infantile hemangiomas is the most common benign vascular tumors of childhood, characterized by rapid proliferation after birth and slow involution thereafter. Although several signaling pathways have been implicated in hemangiomas neovascularization, the mechanism is still unrevealed especially the initiative factor. Here we used gene microarray to profile proliferating and involuting phases of infantile hemangiomas and bioinformatic methods to find the distinguished genes. Log2FC>0.585 or <-0.585 and a nominal P value of 0.05 were used as the filtering criteria. A total of 354 significant genes were identified including 262 upregulated genes. 20 genes were selected for screening according to the microarray results. Trim29 was certified to be responsible for the proliferation of IH using Celigo cytometer method, which were reinforced in patient lesions. By overexpression of Trim29, proteomics was used to detect the downstream proteins.After comparing with the microarray results, HMOX1 was identified and selected for further study after reidentification in patient lesions. Through overexpression and knockdown assay in vitro, we found Trim29 could regulate the expression of HMOX1 and affect hemangiomas neovascularization. Propranolol could block this potential pathway to inhibit proliferation of IH in vivo. These results indicated Trim29 could regulate hemangiomas neovascularization through targeting HMOX1. This innovative pathway could be blocked by propranolol and gave a potential target gene for further investigation to find new drug treatment for IH. Citation Format: Qiang Huang, Wei Li, Xin Ge, Peng Li, Ya Gao. Trim29 regulates hemangiomas neovascularization through targeting HMOX1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2218.