Aim To investigate the effect of long non-coding RNA MIR155 host gene (lncRNA MIR155HG) on proliferation, migration, differentiation and collagen synthesis of myocardial fibroblasts and its molecular mechanism. Methods Mouse myocardial infarction model was constructed. Myocardial fibroblasts were isolated and divided into silent control group, silent MIR155HG group, silent MIR155HG and inhibitor control group, silent MIR155HG and interference miR-133a-3p group, silent MIR155HG and over-expressed Furin group. The expression levels of MIR155HG, miR-133a-3p and Furin were detected by quantitative real-time PCR. Methyl thiazolyl tetrazolium colorimetry was used to detect cell viability. Cell migration was detected by Transwell experiment. Western blot was used to detect the expressions of cyclin D1, cyclin-dependent kinase inhibitor 1A (P21), vascular endothelial growth factor (VEGF), collagen type 1 (Col-1) and α-smooth muscle actin (α-SMA). Targeting relationships between MIR155HG and miR-133a-3p, between miR-133a-3p and Furin were detected by luciferase report experiment. Results In the heart tissue of myocardial infarction model mice, MIR155HG and Furin were highly expressed, and miR-133a-3p was lowly expressed (P＜0.05). After inhibiting MIR155HG expression, the cell viability, migration cell number and cyclin D1, VEGF, Col-1, α-SMA expression levels of myocardial fibroblasts were significantly decreased, while P21 expression level was significantly increased (P＜0.05). MIR155HG targetedly regulated miR-133a-3p, and miR-133a-3p targetedly regulated Furin. Inhibition of miR-133a-3p expression and overexpression of Furin reversed the inhibition effect of inhibiting MIR155HG expression on proliferation, migration, differentiation and collagen synthesis related proteins of myocardial fibroblasts. Conclusion Inhibition of MIR155HG expression can inhibit the proliferation, migration, differentiation and collagen synthesis of myocardial fibroblasts, which may be related to the regulation of miR-133a-3p/Furin axis.