In our study, we found that knockdown of CD155 promoted p38 phosphorylation in HCC cells, and both p38 MAPK inhibitor and shRNA targeting p38α in CD155 knockdown cells resulted in enhanced cell growth and aggressiveness, which revealed a potential tumour‐suppressor role of p38 MAPK as the downstream molecule of CD155 in HCC. Here, MAPK14 is linked to neoplasm.