The invention relates to a method of inducing a human fibroblast to reprogram the human fibroblast into an osteoblast by utilization of Runx2 and a low-molecular-weight compound, particularly relates to a method of inducing a human fibroblast to transdifferentiate the human fibroblast into an osteoblast under the existence of dexamethasone by utilization of Runx2 gene expression, a low-molecular-weight compound CHIR99021 and/or a low-molecular-weight compound forskolin, and belongs to the fields of cytobiology and tissue engineering. The method includes: constructing a human skin fibroblast infected by a slow virus carrying Runx2-GFP, performing transdifferentiation of the human fibroblast under the existence of the dexamethasone by utilization of the low-molecular-weight compound CHIR99021 having a concentration of 5-10 muM and the low-molecular-weight compound forskolin having a concentration of 10 muM, changing into an osteoblast inducing liquid after 7-15 days, and inducing, and the fibroblast can be induced into the osteoblast after 5-20 days. The method can obtain osteoblasts simply and rapidly and can be used for cell therapy for bone metabolic disease, fracture, and the like. A pharmaceutical composition provided by the invention can be used for research, development and production of tissue-engineered bone, brings convenience to fundamental research and brings a prospect for clinical application.