Despite the contradictory effect of TGF‐β1 on HCC initiation and progression, TGF‐β1 promotes HCC progression and metastasis by creating an inflammatory, fibrotic, and immunosuppressive environment that has been well documented.[37] For Tregs, TGF‐β1 is indispensable, as it controls the differentiation and inhibitory function of Tregs.[21] Our study screened that TGF‐β1‐Smad2/3/4 signaling was an upstream activator of SOX12 transcription in HCC cells. Here, SMAD2 is linked to hepatocellular carcinoma.