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CTP synthase (CTPS) can aggregate into an intracellular macrostructure, the cytoophidium, in various organisms including human cells. Previous studies have shown that assembly of human CTPS cytoophidia may be correlated with the cellular metabolic status, and is able to promote the activity of CTPS. A correlation between the cytoophidium and cancer metabolism has been proposed but not yet been revealed. In the current study we provide clear evidence of the presence of CTPS cytoophidia in various human cancers and some non-cancerous tissues. Moreover, among 203 tissue samples of hepatocellular carcinoma, 56 (28%) samples exhibited many cytoophidia, whereas no cytoophidia were detected in adjacent non-cancerous hepatocytes for all samples. Our findings suggest that the CTPS cytoophidium may participate in the adaptive metabolism of human hepatocellular carcinoma.CTPS forms the cytoophidium in various human cancers and some non-cancerous tissues.CTPS cytoophidia are observed in HCC tissues in 28% of patient samples, but not in adjacent non-cancerous hepatocytes.HCC tissues with many CTPS cytoophidia exhibit significantly higher HSP90 level than samples expressing no CTPS cytoophidium.