The application relates to the technical field of molecular diagnosis, in particular to a marker for predicting the risk of COVID-19 severe cases and application thereof. The marker comprises at least N markers selected from VSIG4, KLRK1, TREML1, SAMD14, GIMAP5, SAMSN1, CD160, DGKH, PXYLP1, NUDT16, CMTM5, CSGALNACT2, TMED8, RASGEF1A, UHRF1, GIMAP7, SIRT5, EGFL7, JDP2, IRF2BPL, SIPA1L2, TRABD2A, CKAP4 and TEX2, and N is an optional positive integer from 1 to 24. The above marker can be used to more accurately evaluate the risk of COVID-19 severe cases, and is of great significance for rapidly evaluating the risk of COVID-19 severe cases and seeking a suitable treatment scheme.