Post-transcriptional regulation and RNA-binding proteins (RBPs) play vital roles in the occurrence of secondary injury after intracerebral hemorrhage (ICH). Therefore, we identified RBPs distinctively expressed after ICH by screening and determined thioredoxin1 (Txn1) as one of the most distinctive RBPs. We employed an ICH model and in vitro experiments to investigate the role of Txn1 in ICH. Firstly, we found that Txn1 was mainly expressed in microglia and neurons in the central nervous system, and its expression was significantly reduced in perihematomal tissue. Additionally, adeno-associated virus (AAV) carrying Txn1 was injected into the ICH rat model. Our results showed that overexpression of Txn1 reduced secondary injury and improved outcome in the ICH rat model. Moreover, to understand the therapeutic mechanism of Txn1 after ICH, we performed RNA immunoprecipitation combined with high-throughput sequencing. The results showed that Txn1 binds to inflammation- and apoptosis-related mRNAs and affects gene expression through RNA splicing and translation. Finally, RNA pull-down assays and in vitro experiments confirmed that Txn1 binds to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), leading to reduced inflammation and apoptosis. Our study suggests that Txn1 is a potential therapeutic target for alleviating ICH-induced brain injury.