Objective To analyze the clinical features in adult patients admitted to our hospital with infection of Epstein-Barr virus (EBV) and explore the predictive factor of hemophagocytic Lymphohistiocytosis(HLH). Method The cli-nical data of adult patients with infection of EBV treated in the Shenzhen People's Hospital from September 2016 to September 2019 were collected and analyzed. The patients were divided into two groups, including 56 cases of infectious mononucleosis(IM),12 cases of combined with HLH. Univariate analysis and logistic regression analysis were conducted to identify independent predictive factors for HLH in adults with infection of EBV. Result A total of 68 patients were analyzed, including 33 males [mean age (25.1±7.16) years] and 35 females [mean age (21.83±9.25) years]. Thirty-seven patients(30.6%) had typical triads (fever, sore throat, cervical lymphadenopathy).Increased WBC count was found in 26 cases (38.2%), lymphocyte ratio(LY%)≥50% in 52 cases (76.5%), abnormal lymphocyte ratio≥10% in 20 cases (46 cases accounted for analysis, 43.5%), liver injury in 61 cases (89.7%),spleen enlargement in 43 cases(63.2%), liver enlargement in 9 cases (13.2%). The median value of EBV-deoxyribonucleic acid(EBV DNA) was 5.59×103copies/ml. There was no statistically significant difference in sex, age, the proportion of fever and sore throat symptoms, the proportion of lymphadenectasis、splenomegaly or rash, the proportion of leukocytosis, the proportion of WBC in the normal range, the proportion of a decrease in hemoglobin(HGB), the proportion of abnormal lymphocyte ratio≥10%, the proportion of LDH≥1000U/L and the proportion of alanine ALT≥5 and 10 times the normal value between the two groups (P>0.05). There have statistically significant differences in the PLT decreased, the proportion of the (LY%≥50%, the proportion of serum ferritin increased(respectively greater than 500, 800, 1000, 1500μg/L accounted for analysis), the proportion of ALT/AST≤1, the proportion of EBV DNA≥1.0×105copies/ml between the two groups(P<0.05). Logistic regression analysis showed that patient age, WBC<4×109/L, PLT<10×109/L, LY%≥50%, ALT/AST≤1 and EBV DNA≥1.0×105copies/ml were independent predictive factor for HLH in adults with infection of EBV(OR=1.111, P=0.009; OR=0.033, P=0.027; OR=0.967,P<0.001;OR=0.890,P<0.001; OR=0.006,P=0.001; OR=1.000,P=0.019). Conclusion Adult persons with infection of EBV had atypical symptoms. Patient age, WBC<4×109/L, PLT<10×109/L, LY%≥50%, ALT/AST≤1 and EBV DNA≥1.0×105copies/ml were independent predictive factor for HLH in adults with infection of EBV.