The validity of the constructed HCC organoid model grown spontaneously without CoCl2 was confirmed by the upregulated expression of HIF-1A and its downstream glycolytic genes obtained from the RNA-seq enriched pathways, which resulted in higher glucose consumption, intracellular pyruvate, lactate dehydrogenase expression, and extracellular lactate production. Here, HIF1A is linked to hepatocellular carcinoma.