To study the expression of RPS21 in hepatocellular carcinoma（HCC）and its relationship with immune invasion and prognosis.

A total of 108 HCC patients from August 2018 to December 2022 were retrospectively included as study subjects. Immunohistochemistry（IHC）and reverse transcriptional quantitative polymerase chain reaction（RT-qPCR）were used to detect the expression of RPS21 protein and mRNA in HCC tissues and corresponding paracancer tissues（>5 cm from the margin of cancer tissue）. The data was processed by SPSS 20.0 software. χ² test or Rank Sum test were used to analyze the relationship between RPS21 and clinicopathologic features，Kaplan-Meier survival curve was used to analyze the relationship between RPS21 expression and prognosis，and Spearman Rank correlation was used to analyze the correlation between RPS21 expression and immune infiltration level. P<0.05 was considered statistically significant.

IHC and RT-qPCR results showed that the positive expression rate of RPS21 protein in HCC tissues was significantly higher than that in paracancer normal tissues（84.3%vs.27.8%，P<0.05），and compared with paracancer normal tissues，The expression of RPS21mRNA was significantly up-regulated in HCC tissues［（10.1±1.1）vs.（5.5±0.8），P<0.05］. The high expression of RPS21 was significantly correlated with TMN stage and Edmondson grade（P<0.05）. Spearman rank correlation analysis showed that Expression of RPS21 in HCC is associated with tumor macrotropia in CD4⁺ tumor infiltrating lymphocytes（CD4⁺TILs），CD8⁺TILs，Foxp3⁺ regulatory T lymphocytes（Foxp3⁺Trges），CD11c⁺ dendritic cells（CD11c⁺DCs），and CD163⁺ The infiltration number of macrophages（CD163⁺TAMs）was positively correlated（P<0.05）. After a median follow-up of 33 months，Kaplan-Meier analysis showed that the cumulative overall survival rate and disease-free survival rate of the high RPS21 expression group were significantly lower than those of the low RPS21 expression group（65.4%vs.81.5%，61.7%vs.77.8%）. The differences were statistically significant（P=0.041，0.044）.

RPS21 is highly expressed in HCC tissues，and the high expression of RPS21 is closely related to TMN stage，Edmondson grade，immune invasion and prognosis of HCC. RPS21 may be involved in the occurrence and development of HCC，and may also be involved in immune regulation.