Abstract: Disclosed herein are low immunogenic human anti-TNF-?antibodies which can inhibit the apopotosis of cells induced by TNF-?. The invented low immunogenic human anti-TNF-? antibodies are capable of binding to TNF-? specifically. The invention presents the human anti-TNF-?antibodies which bind to TNF-? with similar affinities as Adalimumab. Most importantly, the invented human anti-TNF-? antibodies showed reduced immunogenicities in vivo, which made them safer candidate for antibody drug and other biotherapy. The invention also features method of de-immunogenicity of antibody drugs by identification, replacement of high immunogenic FR sequence(s) of the human antibody with low immunogenic FR sequences from other human IgGs, and significantly reduce the risk of human anti-human immunogenicity and improve the efficacy of antibody drugs.