Interferon inducible transmembrane protein 3 (IFITM3) is a double transmembrane protein. As a member of the IFITM family, IFITM3 can be upregulated by interferon (IFN) to be involved in various biological processes. In order to determine whether gene expression profiles can be altered by a lack of IFITM3, the present study used shRNAs lentivirus for knocking down the endogenous expression of IFITM3 in human HeLa cells and human whole genome microarrays to obtain gene expression profiles. A total of 1,011 downregulated transcripts and 615 upregulated transcripts were identified using the Agilent expression platform. The identified transcripts were involved in multiple pathways, including the complement pathways, and the antigen processing and presentation pathway. The present study identified the transcripts, which were affected by the downregulation of endogenous IFITM3 and the pathways they were involved in. These findings may lead to an improved understanding of the biological functions of IFITM3.