Objective To explore the therapeutic effect of micro-autologous fat transplantation (MAFT) based on anatomical sub-unit principle of mid-face deep fat tissue in mid-face volumetric augmentation operation. Methods From August 2014 to February 2016, 46 patients suffering volumetric defect of mid-face were divided into the research group and the control group with 23 in each. The MAFT method was used in the two groups. Patients in the research group underwent fat transplatation based on anatomical sub-unit principle of mid-face deep fat tissue, of whom 16 accepted fat transplantaion in suborbicularis oculi fat area, 23 in deep media cheek fat area and 13 in buccal fat area. Patients in the control group accept conventional fat transplantation method; the fat granule were uniformly transplanted to the deep and superficial mid-face fat tissue. The curative effiency and patients' satisfaction were compared between the two groups. Results The curative effiency and patients' satisfaction of the research group (91.3%, 82.6%) were better than those of the control group (60.9%, 43.5%), and there were significant differences (P<0.05). All patients were followed up for 6 months to 2 years, with an average of 1 year. No complication occurred in both groups. Conclusion The MAFT operation based on anatomical sub-unit principle of mid-face deep fat tissue could precisely perform mid-face volumetric augmentation and rejuvenation.