摘要Background:Within the tumor microenvironment,survival pressures are prevalent with potent drivers of tumor progression,angiogenesis,and therapeutic resistance.N6-methyladenosine(m6A)methylation has been recognized as a critical post-transcriptional mechanism regulating various aspects of mRNA metabolism.Understanding the intricate interplay between survival pressures and m6A modification pro-vides new insights into the molecular mechanisms underlying hepatocellular carcinoma(HCC)progres-sion and highlights the potential for targeting the survival pressures-m6A axis in HCC diagnosis and treat-ment.Data sources:A literature search was conducted in PubMed,MEDLINE,and Web of Science for relevant articles published up to April 2024.The keywords used for the search included hepatocellular carcinoma,cellular survival,survival pressure,N6-methyladenosine,tumor microenvironment,stress response,and hypoxia.Results:This review delves into the multifaceted roles of survival pressures and m6A RNA methylation in HCC,highlighting how survival pressures modulate the m6A landscape,the impact of m6A modifica-tion on survival pressure-responsive gene expression,and the consequent effects on HCC cell survival,proliferation,metastasis,and resistance to treatment.Furthermore,we explored the therapeutic potential of targeting this crosstalk,proposing strategies that leverage the understanding of survival pressures and m6A RNA methylation mechanisms to develop novel,and more effective treatments for HCC.Conclusions:The interplay between survival pressures and m6A RNA methylation emerges as a complex regulatory network that influences HCC pathogenesis and progression.