BackgroundHepatocellular carcinoma (HCC) is one of the most common human cancers with poor prognosis in the world. HCC has become the second leading cause of cancer-related death in China. It is urgent to identify novel biomarker and valid target to effectively diagnose, treat or predict the prognosis of HCC. It has been reported that S100A family is closely related to cell proliferation and migration of different cancers. However, the values of S100As in HCC remain to be further analyzed.MethodsWe investigated the transcriptional and translational expression of S100As, as well as the value of this family in HCC patients from the various databases.ResultsS100A10 was most relevant to HCC.ConclusionsThe results from HCC patients’ tissues and different cells also confirmed the role of S100A10 in HCC. Furthermore, we proved that S100A10 could influenced the cell proliferation of HCC cells via ANXA2/Akt/mTOR pathway. However, it would appear that the relationship between S100A10 and HCC is complex and requires more research.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12885-023-11127-3.