Curcuma sahuynhensis Škorničk. & N.S. Lý is an indigenous plant in Vietnam that is used as spices and medicine to treat diseases related to digestive disorders. This study was designed to evaluate, for the first time, the in vitro and in silico anticancer effect of the ethyl acetate extracts from C. sahuynhensis leaves and rhizomes against different cancer cell lines and their chemical constituents. The volatile constituents of the ethyl acetate extracts were analyzed by gas chromatography-mass spectrometry (GC–MS). The cytotoxic effect was tested against five cancer cell lines by the Sulforhodamine B and MTT methods, as well as a molecular docking study. The volatile components analysis indicated that the leaf and rhizome extracts contained twelve and eight components, respectively. The predominant volatile constituents, including diisooctyl phthalate; neophytadiene; 3,7,11,15-tetramethyl-2-hexadecen-1-ol; acetic acid, 3,7,11,15-tetramethyl-hexadecyl ester; isoborneol; methyl palmitate, were found in the leaf extract. Meanwhile, eucalyptol; ambrial; (E)-labda-8(17),12-diene-15,16-dial; α-copaene; trans-β-ionone; isolongifolol, acetate; and isobornyl formate were the main components in the rhizome extract. On five human cancer cell lines (MFC-7, SK-LU-1, Hela, MKN-7, and HL-60), the leaf and rhizome extracts showed concentration-dependent manner cytotoxic activity, with IC50 values ranging from 126.11±8.27 to 254.82±10.25 µg/mL for leaf extract and IC50 values ranging from 109.30±6.75 to 184.59±10.24 µg/mL for rhizome extract. Compounds (E)-labda-8(17),12-diene-15,16-dial (19), isolongifolol, acetate (10) and diisooctyl phthalate (20) were identified as potential inhibitors of epidermal growth factor receptors based on computational analysis. The findings of this work might offer an experimental foundation for further research on the isolation of metabolites and their in vivo cytotoxicity related to "vegetable turmeric" resources.