Homeobox D10 (HOXD10) belongs to the human homeobox (HOX) gene family, and the homologous protein encoded by HOX primarily controls cell differentiation and morphogenesis during embryonic development. The current study aimed to explore the roles and mechanisms of HOXD10 in the migration of human fibroblast-like synoviocytes in rheumatoid arthritis (RAFLS). Cell counting kit-8, cell migration and wound healing assays were performed to examine the cell viability and migration, respectively. Western blot and reverse transcription-quantitative polymerase chain reaction assays were used to evaluate the association between mRNA and protein expression levels. The results revealed HOXD10 expression was upregulated in tissues from patients with RA. HOXD10 silencing inhibited the viability of RAFLS. In addition, HOXD10 silencing suppressed the migration of RAFLS through modulating the expression of cadherin-11, N-cadherin, E-cadherin, vimentin, zonula occludens-1, integrinβ1 and paxillin. In conclusion, HOXD10 silencing downregulates the p38/c-Jun N-terminal kinase signaling pathway, which in turn may suppress the migration of RAFLS.