TC-325 powder has been successfully used in the management of malignancy-related upper gastrointestinal bleeding (UGIB) with favorable results. We conducted a meta-analysis of randomized controlled trials (RCTs) comparing TC-325 hemostatic powder with standard endoscopic treatments in the management of malignancy-related UGIB. Several databases were reviewed from inception to May 02, 2024 to identify RCTs comparing TC-325 and standard endoscopic treatments for the management of malignancy-related UGIB. Our outcomes of interest were immediate hemostasis, 30-day rebleeding, length of hospital stay, need for surgery, need for angiographic embolization, and all-cause mortality. We calculated pooled risk ratio (RR) with 95% confidence intervals (CI) for categorical variables and mean difference (MD) with 95% CI for continuous variables. We used a random effect model to analyze the data and heterogeneity was assessed by I2 statistic. Four RCTs with 227 patients were included. We found that, the rate of immediate hemostasis was significantly higher in the TC-325 group compared to the standard therapy group, RR (95% CI): 1.48 (1.26, 1.74). There was no significant difference in 30-day rebleeding between the groups RR (95% CI): 0.52 (0.15, 1.76). We found no significant difference in other outcomes between groups such as the need for angiographic embolization, all-cause mortality, length of hospital stay, and need for surgery. We found that, TC-325 hemostatic powder was superior to standard endoscopic treatments in achieving immediate hemostasis in patients with malignancy-related UGIB.