Context: Cancer is one of the leading causes of death throughout the world. Treatment failure in cancer can be caused due to drug resistance and toxicity. Therefore, it is necessary to develop new drugs that have relatively smaller side effects, one of which is by screening natural ingredients. One of the plants that have the potential for anticancer therapy is red betel (Piper crocatum). Aims: The purpose of this study was to determine the potential of methanolic extract of P. crocatum leaf

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... PcL) as a cytotoxic agent and phytochemical screening of MEPcL. Settings and Design: This research was conducted at using The Post Test Only Control Group Design. Methods and Material: Phytochemical screening was carried out by tube test and TLC, while the Brine Shrimp Lethality Test and cytotoxicity tests were carried out by direct counting method. Statistical analysis used: Pearson correlation test was used to analyze the cytotoxic effects and IC50 with probit analysis. Results: Based on the results of phytochemical screening, MEPcL contained flavonoids, tannins, alkaloids, saponins, and terpenoids. The results of the study showed that the LC50 value of MEPcL was (70.013 ± 3.874 2) µg mL -1 on BST and IC50 value was (34.20 ± 1.480 6) µg mL -1 on HeLa cell lines. Conclusions: Based on explanation above, it can be concluded that MEPcL has potency to be developed as anticancer agent.