In vivo, ASPDH overexpression suppressed tumor growth, decreased nuclear p65 and PD-L1, and increased cytoplasmic p65, alongside reduced lactate secretion and NF-κB/PD-L1 modulation.<h4>Conclusion</h4>ASPDH inhibits liver cancer cell proliferation, migration, and invasion by downregulating lactate secretion and suppressing the NF-κB/PD-L1 signaling pathway. Here, CD274 is linked to liver cancer.