Pediatric Risk of Mortality Score (PRISM III-12) is a physiology-based predictor for risk of mortality. We conducted prospective study from January 1, 2014 to 2015 in pediatric oncology intensive care unit (POICU) at South Egypt Cancer Institute, Egypt to explore the ability of 1st PRISM III-12 to predict the risk of mortality in critically ill cancer patients and the ability of serial PRISM III measured every 72 hours to follow-up the patients’ clinical condition during POICU stay. In total, 123 (78 males) children were included. Median age was 5 years (1 to 15 y). Death rate was 20%. 1st PRISM III-12 mean was 19 (0 to 61). The mean 1st PRISM III-12 for survivors was significantly higher compared with nonsurvivors (15 vs. 37 respectively; P<0.001). 1st PRISM III-12 mean was significantly correlated to the reasons for admission and organ failures’ number (P<0.001 and <0.001). 1st PRISM III-12 correlated weakly positive with the length of stay (r=0.2; P=0.024). Receiver operator curve for 1st PRISM III-12 was 0.913 (95% confidence interval, 0.85-0.98; P<0.001). Decline in serial PRISM III was significantly correlated with favorable (survivor) outcome (P<0.001). We concluded that PRISM III-12 can be used effectively in predicting the risk of mortality and following the clinical condition of patients during POICU stay.