【Objective】To determine whether activated hepatic stellate cell（HSC）become quiescent phenotype if cultured in a soft extracellular matrix（ECM）.【Methods】HSC-T6 cells which stably expressed myofibroblast（MFB） phenotype，were cultured in the 2D and 3D in-vitro matrix culture models that were constructed by 1 mg/mL fibrin gel. The proliferation activity of HSC-T6 was determined by cell counting kit-8（CCK8）assay at different time points（24 h， 48 h，72 h，96 h）. Immunofluorescence and gelatin zymography analysis were performed to detect the expression of α-SMA，MMP-2，and MMP-9. Moreover，the cellular surface morphology and deformability was detected by AFM. 【Results】After cultured in the fibrin gel，the cellular proliferation activity，expression of α-SMA，MMP-2 and MMP-9，and cellular deformability of activated HSC-T6 was obviously down-regulated in contrast to the control group （P<0.05），and there were also differences in the inhibition of cellular proliferation activity，the assembly of α-SMA stress fiber and the effect of cellular deformability between 2D and 3D fibrin gel cultured（P<0.05）.【Conclusions】Soft fibrin gel inhibited the transdifferentiation of activated HSC-T6，but could not make it revert to α-SMA negative quies? cent phenotype.