The ethanol extract of Centaurea aegyptiaca aerial parts afforded two new chlorinated bioactive guaianolides, cenegyptin A (1) and cenegyptin B (2), in addition to four known sesquiterpenes (3 - 6). Their identities were established on the basis of their spectral data. The cytotoxicity (IC50, μM) of compounds 1 - 6 were evaluated against hepatic (HEPG2) and laryngeal (HEP2) carcinoma cell lines in comparison with normal fibroblasts (BHK). Compound 1 showed cytotoxic activity against HEPG2 and HEP2 with IC50 values of 7.2 ± 0.04 and 7.5 ± 0.02, respectively. However, compound 2 exhibited only a limited toxicity against both cell lines.