AIM: To investigate the effect of Physalis angulata leaf extract on apoptotic and proliferation of retinoblastoma cells. Despite several previous studies evidencing the anti-cancer potential of Physalis angulata; however, certain study that proves its benefits in retinoblastoma cancer cells has been limited. METHODS: This study utilizes an in-vitro experimental study by applying Y79 human retinoblastoma cell line culture obtained from the American Type Culture Collection (ATCC; 10801 University Boulevard Manassas, VA 20110, USA). The cell was divided into 4 groups. Group I was the control group without the administration of Physalis angulata leaf extract. Whereas, group II, II and IV are engaged with 25, 50, and 100 μg/mL of Physalis angulata leaf extract respectively. After a 24h incubation, an examination with microtetrazolium (MTT) cell proliferation assay and Annexin V apoptosis detection was conducted. Statistical analysis was performed with the Tukey test. RESULTS: Physalis angulata leaf extract improved apoptosis and significantly reduced the number of living cells in retinoblastoma cells, along with the increase in the given dose. Based on the Tukey test, a significant difference was found in the treatment group at 50 μg/mL (P=0.025) and 100 μg/mL (P=0.001) in the measurement of apoptosis. Proliferation measurements also indicated a significant decrease in the number of living cells in the 50μg/mL treatment group (P=0.004), and in the 100 μg/mL treatment group (P=0.000). Meanwhile, a dose of 25 μg/mL indicated insignificant difference in the two measurements. Improved apoptosis and decreased number of living cells occured at a dose of 100 μg/mL. Decreased number of living cells (in the measurement of proliferation) was due to the inhibited proliferation or improved apoptosis. CONCLUSION: Physalis angulata leaf extract improve apoptosis in retinoblastoma cell culture, requiring further research to inhibit proliferation.