Hundreds of circular RNAs (circRNAs) have been identified as key regulators in biological processes; however, only few of these circRNAs have been functionally described to participate in the development of hepatocellular carcinoma (HCC). The present study aimed to reveal the function and molecular mechanisms of circ_0124208 in HCC. Real-time quantitative PCR revealed the upregulation of circ_0124208 in HCC tissues and cells. Based on cell functional experiments, silencing circ_0124208 attenuated proliferation and migration, but boosted the apoptosis of Hep 3B and Huh7 cells in vitro. The in vivo experiment further validated the repression of tumor growth via circ_0124208 knockdown. RNA immunoprecipitation and dual-luciferase reporter assays showed that circ_0124208 sponged miR-338-3p and reduced its expression. miR-338-3p inhibition was found to partially reverse the tumor-suppressive effects caused by circ_0124208 in Hep 3B and Huh7 cells. Furthermore, miR-338-3p directly targeted laminin subunit gamma 1 (LAMC1). The malignancy of Hep 3B and Huh7 cell was decreased by LAMC1 knockdown, and this effect was mitigated by miR-338-3p suppression. Overall, circ_0124208 was demonstrated for the first time to play a crucial role as an oncogene in HCC, implying that it could be a useful biomarker for HCC diagnosis. Furthermore, the circ_0124208/miR-338-3p/LAMC1 axis can be used as a potential therapeutic target for HCC treatment.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.