Pulmonary silicosis is an irreversible and untreatable disease that is characterized by interstitial lesions and perpetual fibrosis in the lungs. This study was performed to determine whether mesenchymal stem cells (MSCs) and hepatocyte growth factor (HGF) could exhibit therapeutic effects on human silicosis. This non-randomized uncontrolled trial comprised four patients with pulmonary silicosis who had developed lung fibrosis and received autologous bone marrow MSCs previously transfected by a vector containing human HGF cDNA (MSCs/HGF). MSCs/HGF were intravenously administered weekly for three consecutive weeks at a dose of 2 x 10(6) cells/kg. Pulmonary function, high kilo-voltage chest X-ray radiography, computed tomography (CT) scan, and peripheral blood lymphocyte subset and serum IgG concentrations were evaluated after cell therapy. The treatment was found to be generally safe. Symptoms such as cough and chest distress gradually ameliorated at six months post-therapy, accompanied by the significant improvement of pulmonary function. The ratios of the peripheral CD4- and CD8- positive cell concentrations were increased (P < 0.05). Furthermore, the serum IgG levels in these patients were decreased and reached the normal range (P < 0.05). CT scans showed partial absorption of the nodular and reticulonodular lesions in the lungs during follow-up of at least 12 months. The effectiveness of this novel regimen observed in these patients suggests that a placebo-controlled clinical trial needs to be developed. This study carries trial registration No. NCT01977131 (ClinicalTrials.gov).