Zanthoxylum nitidum (Roxb.) DC., is one of Guangxi's characteristic national medicines, and is the classic Laoban medicine of Yao people “Ru Shan Hu” and Zhuang medicine “Liang Bei Zhen”. It has been used as an anti‐inflammatory, analgesic and haemostatic medicine for thousands of years. In this study, four new sesquiterpenoids (1–4), along with six previously described coumarins (5–10), were isolated from 95 % EtOH extract of Zanthoxylum nitidum. Comprehensive spectroscopic analyses (NMR and HR‐ESI‐MS) were used to elucidate the structures of these isolates. The absolute configurations of nitidumine A–D (1–4) were established by electronic circular dichroism (ECD). Their cytotoxicity of all the isolates against five cancer cell lines (T24, HeLa, MGC‐803, A549, and HepG2) was evaluated by MTT experiment and found not to be cytotoxicity.