The feasibility of silk fibroin protein (SF) scaffolds for tissue engineering applications to promote cell proliferation has been demonstrated, as well as the ability to mimic natural extra-cellular matrix (ECM), SF/chitosan (CS), a polysaccharide, scaffolds for tissue engineering. However, the response of cells to SF/CS–hyaluronic acid (SF/CS–HA) scaffolds has not been examined, which this study attempts to do and then compares those results with those of SF scaffolds. SF/CS–HA microparticles were fabricated to produce scaffolds in order to examine the proliferations of human dermal fibroblasts (HDF) in the scaffolds. Positive zeta potentials and ATR-FTIR spectra confirmed the co-existence of SF and CS–HA in SF/CS–HA microparticles. HDF proliferated well and migrated into SF/CS–HA scaffolds for around 160 μm in depth, as well as those in SF scaffolds after 7 days of cultivation, as observed using confocal microscopy. Interestingly, HDF grown in SF/CS–HA scaffolds had a markedly higher cell density than that in SF ones. Additionally, MTT assay revealed that the growth rates of HDF in SF/CS–HA scaffolds significantly exceeded ( P  < 0.01, n  = 5) those in scaffolds of SF and SF/CS. The daily glucose consumptions and lactate formations, metabolic parameters, of HDF grown in SF/CS–HA and SF/CS scaffolds were significantly higher ( P  < 0.01, n  = 3) than those in SF ones in most culturing days. Results of this study suggest that SF/CS–HA scaffolds have better cell responses for tissue engineering applications than SF ones.