Background <p>Globally, HCC is still one of the most common cancers. N6-methyladenosine (m⁶A) modifications and long-stranded noncoding RNAs (lncRNAs) play key roles in regulating HCC progression. The role of the lncRNA RNF144A-AS1, a newly identified lncRNA, in HCC is unclear.</p> Methods <p>In HCC, RNF144A-AS1 expression level and its effect on prognosis were investigated by bioinformatics. CCK-8, EdU, scratch assay, and Transwell assays were used to detect the impact of RNF144A-AS1 on hepatocellular carcinoma malignancy. Assays using MeRIP-qPCR, RIP, and Actinomycin D were used to study the effects of m⁶A methylation on hepatocellular carcinoma malignant phenotypes. Revealing the potential mechanism of action of RNF144A-AS1 by luciferase reporter gene assay, PCR, and Western blot assays, and Nude mice subcutaneous load cell and lung metastasis models were used to verify the effect of RNF144A-AS1 on the malignant phenotype of tumors in vivo.</p> Results <p>The lncRNA RNF144A-AS1 was significantly upregulated in HCC, and it was significantly associated with poor prognosis. Functionally, HCC cells with RNF144A-AS1 knockdown were inhibited in terms of proliferation, migration, and invasion. Further studies in vivo confirmed that RNF144A-AS1 knockdown inhibited tumor cell growth and metastasis. Mechanistically, METTL3 increased the m⁶A modification and stability of RNF144A-AS1 in an IGF2BP1-associated manner. In addition, RNF144A-AS1 was inhibited by sponge-like miR-1301-3p to inhibit RNF38 degradation, thereby promoting the HCC malignant phenotype.</p> Conclusion <p>The RNF144A-AS1 gene is affected by METTL3/IGF2BP1 methylation and encourages liver cancer proliferation and metastasis by increasing expression of RNF38 through sponge-like miR-1301-3p. RNF144-AS1 promises to be a therapeutic target for HCC.</p>