Epstein-Barr virus (EBV) infection is associated with many cancers pathogenesis, especially nasopharyngeal cancer (NPC). This infection has been reported to promote metastatic potential via stromal interaction molecule 1 (STIM1). However, the post-transcriptional regulation of STIM1 activities in EBV-related NPC is not well understood yet. This study aims to investigate the post-transcriptional regulatory roles of STIM1silencing in EBV-related NPC. C666-1 cells is an NPC cell line model harbouring EBV. The C666-1 cells were transfected with Dicer substrate short interfering RNA (DsiRNA) targeting STIM1for 48 and 72 h periods. The expression of STIM1 and a set of microRNAs were determined via qRT-PCR. The post-translational expressions of RAC1 and CDKN1B proteins were determined via western blot profile. The functional profile of STIM1silencing showed inhibition of C666-1 cells proliferation and migration activities. Our molecular finding suggests that STIM1silencing could promote tumor suppressor activities via miR-375 and CDKN1B expression.This study suggests that STIM1silencing could suppress the survival of EBV-related NPC cells via post-transcriptional regulation of miR-375 and miR-200a-3p as well as post translational regulation of RAC1 and CDKN1B proteins. Further comprehensive work is needed to support this finding especially involving in vivo work.