DHX34 is an ATP-binding RNA helicase that functions primarily in nonsense-mediated decay (NMD), a quality control mechanism degrading mRNAs with premature stop codons 1. DHX34 promotes UPF1 phosphorylation and interacts with key NMD proteins UPF2 and EIF4A3 to facilitate mRNA degradation 2. Beyond NMD, DHX34 associates with the spliceosomal C complex and regulates alternative splicing at exon-intron boundaries, establishing a dual role in gene expression control 3. DHX34 and NBAS participate in autoregulatory NMD feedback loops that modulate cellular stress response and membrane trafficking pathways across species 4. Clinically, germline DHX34 variants are associated with familial myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) predisposition 5. DHX34 loss-of-function impairs hematopoietic differentiation, explaining AML/MDS susceptibility 3. In pan-cancer contexts, DHX34 is highly expressed and correlates with poor prognosis in multiple tumors; cadmium exposure upregulates DHX34 to promote lung cancer progression 6. Conversely, DHX34 deficiency in hepatocellular carcinoma triggers dsRNA accumulation and type I interferon responses, activating anti-tumor immunity 7. These findings suggest DHX34 as a therapeutic target for both cancer prevention and immunotherapy enhancement.