The present invention belongs to the field of antibody engineering, and provides a fully human-derived anti-PD-1 monoclonal antibody, a preparation method thereof, and use thereof. After obtaining a monoclonal antibody of anti-PD-1 by screening from a fully synthetic antibody library, the library for mutation of light chain CDR1-3 region and heavy chain CDR1-3 region of the obtained antibody by affinity maturation technique Are sequentially constructed and screened to obtain high affinity anti-PD-1 antibodies. The antibody can be used to treat tumors, inflammations, and autoimmune diseases. [Selection] Figure 16本発明は抗体工学の分野に属し、完全ヒト由来の抗PD-1のモノクローナル抗体、その調製方法および用途を提供している。完全合成抗体ライブラリからスクリーニングして抗PD-1のモノクローナル抗体を得た後、親和性成熟技術によって、得られた抗体の軽鎖CDR1-3領域と重鎖CDR1-3領域との突然変異についてライブラリを順次構築し、スクリーニングして高親和性の抗PD-1の抗体を獲得する。前記抗体は、腫瘍、炎症、自己免疫疾患の治療に用いることができる。【選択図】図16