The invention discloses small interfering nucleic acid as well as a composition and application thereof. The invention claims to protect siRNA, which is PP-1758, PP-17660, PP-20091, PP-20163, SP-26, SP-179, SP-2013, SP-2867, SP-3169, SP-3552, MG-83, NP-208 or NP-241, wherein a part of nucleotides of the positive-sense strand are 2 '-O-methyl ribonucleotides, and a part of phosphate groups are thiophosphate groups. The invention provides brand new siRNA and a composition thereof. The brand new siRNA and the composition thereof can effectively prevent and/or treatment novel coronavirus.