Nasopharyngeal carcinoma (NPC) has a high incidence rate. It is a major public health burden in endemic areas. NPC is associated with considerable morbidity and mortality, so better treatment is needed. Scutellarin (SL) is an anticancer agent extracted from medicinal plants and it exerts anti-cancer effects through various signaling pathways. However, Scutellarin’s underlying anti-proliferative and apoptotic mechanisms remain largely unknown. Thus, the current study intended to explore the molecular action of in vitro SL on CNE1 and CNE2 human NPC cells. MTT assay, DCFH-DA, Rh-123 staining, DAPI staining, flow cytometry, likewise Western blot analysis were employed to assess the proliferation and apoptosis Of NPC cells (CNE1 and CNE2) were administered SL (20 and 30 µM). Possible molecular mechanisms; intracellular ROS, MMP, cell cycle distributions, cell-cycle regulatory proteins, and MAPKs/NF-κB signaling were assessed. It was found that SL could inhibit NPC cells proliferation via enhanced intracellular ROS, MMP loss, and trigger apoptosis. SL prompted G0/G1 arrest in NPC cells by subduing cell cycle allied proteins; cyclin D1, CDK4/CDK6, pRB, and MAPKs/NF-κB signaling. Our investigation provides proof that MAPKs/NF-κB route is a possible target for treatment and may be essential in the SL-actions that are mediated against nasopharyngeal carcinoma malignancy.