Here, we provided the evidence how activated HSCs enhanced tumor progression of heat-treated residual HCC as the following: (i) activated HSCs-derived condition medium (HSC-CM) aggravated malignant phenotypes of heat-exposed residual HCC cells (ii) periostin (POSTN) mediated the tumor-promoting effects of HSC-CM (iii) vitamin D analog calcipotriol blocked POSTN secretion from activated HSCs (iv) calcipotriol plus cisplatin suppressed the in vivo activated HSCs-promoted tumor progression of the residual HCC cells via inhibition of POSTN expression and an increase of apoptosis. The gene discussed is POSTN; the disease is hepatocellular carcinoma.