The invention discloses a research and development method of siRNA for COVID-19 virus drug therapy, which comprises: a first part of preliminarily screening potential high-efficiency siRNA based on multiple indexes, which specifically comprises the following steps: step 1, selecting an S gene sequence as a target sequence; step 2, obtaining a corresponding siRNA double strand; step 3, screening asiRNA sequence with a concentration of 36 to 53%; step 4, screening out siRNA with free energy; step 5, defining and calculating an index I; step 6, screening out siRNA of the first 50%; step 7, defining and calculating an index II; step 8, screening out siRNA with the index II being equal to 5; step 9, defining and calculating an index III; step 10, ranking the first 50% of siRNA; step 11, directly taking all the candidate siRNAs selected in the step 10; step 12, specifically targeting a target sequence; step 13, taking the remaining siRNA as the siRNA subjected to preliminary screening; anda second part of performing interference efficiency prediction and optimization by using a machine learning model. The method has the beneficial effect of realizing safe, reliable and high-interference-efficiency siRNA design.