The invention belongs to the technical field of a long-acting fusion protein medicine, and in particular relates to a fusion protein of a granulocyte colony-stimulating factor (G-CSF) as well as a mutant of the granulocyte colony-stimulating factor (mG-CSF) and a human serum albumin 3rd domain (3DHSA). The amino acid sequence of the human serum albumin 3rd domain of the fusion protein is expressed as SEQ NO: 1, and the amino acid sequences of the granulocyte colony-stimulating factor and mutant thereof are expressed as SEQ NO: 2 and SEQ NO: 3. The invention successfully constructs two fusion proteins for the first time, overcomes the shortcoming of short in vivo half-life period of the granulocyte colony-stimulating factor and provides a novel fusion protein molecule integrating characteristics of the human serum albumin 3rd domain and the granulocyte colony-stimulating factor. The fusion protein disclosed by the invention, on the basis of maintaining G-CSF bioactivity, has in vivo half-life periods of 3.3hours and 4.4hours which are about 1.6 and 2 times as much as the half-life period of the G-CSF, thereby providing an innovative drug molecule having a potential application value.