Collectively, our study reveals a novel crosstalk between HSCs and hepatoma cells via the METTL3/m6A-BMP10-SMAD1/5/8 axis, highlighting a potential therapeutic target for HCC.<h4>Significance</h4>In this study, we found that HSC-specific METTL3 deficiency significantly accelerated HCC progression in the fibrotic liver. This evidence concerns the gene SMAD1 and hepatocellular carcinoma.