Hemophagocytic lymphohistiocytosis (HLH), as a life-threatening hyperinflammatory syndrome, rarely presents as a harbinger of aggressive large B cell lymphoma (LBCL), with a rapidly progressive clinical course and poor prognosis. A total of 30 patients diagnosed with aggressive LBCL concurrent with HLH were retrospectively reviewed in this study. Median age was 60 years (range, 24 to 85 years). Thirteen (43.3%) patients treated with ruxolitinib combined with corticosteroid (Ru-D) regimen achieved the highest overall response rate (ORR) of 84.6%, which was significantly higher than that of 40.0% in the etoposide and corticosteroid group and 33.3% in the corticosteroid group (P = 0.019). The median overall survival (OS) was 16.2 months, with corresponding 1-year and 2-year OS rates of 63.3% and 38.4%, respectively. The 8-week mortality rate was 26.7%. Patients responded to anti-HLH therapy within 2 weeks had significantly better OS than non-responsive group (P = 0.009). Low-intensity chemotherapy without anthracycline as the first-line of anti-lymphoma therapy followed by RCHOP did not compromise survival, and the median OS was 13 months and 19.1 months, respectively (P = 0.457). Ferritin levels ≥ 3606 ng/mL and uncontrolled HLH within 2 weeks were the independent risk factors associated with inferior OS. Our findings highlight the high early mortality and short survival of these patients and underscore the urgent need for developing more effective treatment strategies to improve prognosis.