This study aimed to study the anticancer effects of leaves methanol extract of Rumex crispus using various human cancer cell cultures namely MCF-7, HEPG-2 and HCT116, in vitro using sulforhodamine B (SRB) dye assay. Seven different concentrations of an extract from leaves of Rumex crispus were freshly prepared and used for cytotoxic activity. The leave extracts exhibited significant anti-proliferative activities against all human tumor cell lines whereas the ceased effect of almost RCLME was greater for the human colon cancer cells line (HCT116) than the breast cancer cells (MCF-7) and human liver cancer cells (HepG2). The numbers of dead cells increased from 7.490% for (HCT116) cell line, from 1.797% for (HepG-2) and from 2.80 % for (MCF-7) at concentration (0.01 ug/ml) of RCLME to be 93.94%, 94.81 % and 88.43% respectively at conc. (1000 ug/ml). The results showed also that the decline in the viable cells from conc. at (0.1 to 100 ug/ml) not so sever while the sudden increase in the alive cells found in the conc. (1000 ug/ml) of RCLME. The LC–MS/MS determination was performed directly from the leaves methanol extract of Rumex crispus without derivatization. Betaine, 2-Phenethylamine, Adenine, Apophedrin pyridoxine, Aceclidine, Adenosine, Tolycaine, Jasmolone, Desmosterol and psi-Tectorigenin were identified. In conclusion: Rumex crispus leaves methanol extract could be used as a natural product against various types of cancers. It is recommended to use the RCLME as it, due to chemicals synergetic effect against various types of tumor.