Nasopharyngeal carcinoma (NPC) is a distinctive type of head and neck cancer with the highest incidence in South China. Previous studies have proved that matrine, a main alkaloid isolated from Sophora flavescens Ait, has antitumor activity against NPC. However, the effect is not so pronounced and the underlying mechanism remains largely unclear. Here we investigated whether 14-thienyl methylene matrine (YYJ18) that was derived from matrine could exert more effective suppression activity on NPC, along with the underlying mechanism.