〔Abstract〕 Objective To investigate the effects of miR-138-5 p and TCF4 on the malignant biological behavior of MuM-2 B cells in uveal melanoma. Methods MuM-2 B cells were transfected or co-transfected with miR-138-5 p mimic and pcDNA-TCF4, respectively. A mouse model ofin vivoxenograft tumor was established. Cell transfection efficiency was detected by RT-qPCR. Bioinformatics software predicted miR-138-5 p and TCF4 target sites. Dual luciferase reporter gene assay was used to verify the targeted relationship. Clone formation assay was used to detect the ability of cell clone formation. The invasion ability of cells was detected by Transwell assay. Western blot analysis of TCF4 and epidermal mesenchymal transformation(EMT) related protein expression. Immunohistochemistry was used to detect the expression of Ki67, VEGF and Vimentin in tumor tissues. Results Compared with control group, miR-138-5 p and TCF4 were up-regulated in transfected group(P<0.05). Between miR-138-5 p and TCF4 were target relationship. Overexpression of miR-138-5 p inhibited MuM-2 B cell proliferation, invasion ability as well as up-regulating the protein expressive levels of E-cadherin and Vimentin and down-regulating the protein expressive levels of N-cadherin by targeting TCF4 in Mum-2 B cells(P<0.05). In transplanted tumorsin vivo, overexpression of miR-138-5 p significantly reduced tumor weight(P<0.05), and overexpression of miR-138-5 p down-regulated the positive cell rate of Ki67, VEGF and Vimentin in tumor tissues(P<0.05). Conclusion The overexpression of miR-138-5 p down-regulated the TCF4 levels, and further inhibited the cell proliferation, invasion and EMT of uveal melanin Mum-2 B cells.