Mortality rates of acute lymphoblastic leukemia (ALL) have improved over the past 20 years; however, a significant portion of deaths stems from the lack of prognostic biomarkers, which can direct therapy and overcome drug resistance. microRNA‐155a (miRNA‐155a) and miRNA‐181a are two single‐stranded miRNAs involved in the pathogenesis of many types of leukemia and lymphoma and is linked to drug resistance. We investigated their expression levels in 55 patients, 45 diagnosed with ALL and 10 as a control group. We found that miRNA‐155a and miRNA‐181a were significantly upregulated in the ALL group with both being linked to high levels of minimal residual disease and poor prognosis. miRNA‐155a cutoff value was significant in discriminating between high‐ and low‐risk ALL patients as well as between ALL patients and healthy controls, miRNA‐181a cutoff value, however, was not significant. Both markers levels were significantly downregulated after therapy. We conclude that miR‐155 is correlated with poor prognosis in ALL, whereas we couldn’t link miRNA‐181a to the prognosis in ALL. Moreover, the marked decrease in their expression after therapy could reflect their impact on disease outcome.