ABSTRACT Background Acute myeloid leukemia (AML) is a disease characterized by the proliferation of abnormal cells originating from blood stem cells. Understanding the pathogenesis and progression of AML, as well as identifying molecular markers for early diagnosis and prognosis assessment, is of paramount importance. Methods The AML dataset was obtained from the Cancer Genome Atlas (TCGA), while the normal sample dataset was derived from the Genotype-Tissue Expression(GTEx) dataset. Furthermore, the association between SRSF12 expression and drug response was assessed using the Cancer Therapeutic Response Portal (CTRP) database to evaluate its potential therapeutic value. Finally, SRSF12 expression in AML cells was measured using quantitative real-time PCR (qRT-PCR). Result The difference in SRSF12 expression between 13 types of tumors and normal tissue samples was found to be statistically significant (P < 0.05). SRSF12 exhibited predominantly high expression in AML, indicating its potential as a diagnostic and prognostic marker for AML patients. High expression of SRSF12, along with age and cytogenetic risk, emerged as independent predictors of favorable prognosis in AML patients (P < 0.05). PCR demonstrated a significant increase in SRSF12 expression in AML patients. Conclusion Overall, our findings suggest that the high expression of SRSF12 in AML patients is a poor prognostic factor, which may provide a new option for the diagnosis, and targeted therapy of AML.