Background: Systemic lupus erythematosus (SLE) is most likely to occur during the first and second trimesters of pregnancy. There were few studies focused on the new-onset SLE during the late pregnancy or puerperium. SLE has been considered an important cause of thrombocytopenia. However, lymphoma may also be a cause of thrombocytopenia. Here, we reported a challenging case of new-onset SLE occurred at the gestational age of 33 weeks, and the pregnant woman suffered lymphoma before. Case presentation: A 25-year-old primigravid Chinese woman with a medical history of non-Hodgkin lymphoma (NHL) suffered thrombocytopenia at 30+5 weeks of gestation. Her skin rashes occurred one week later. Her platelet count was decreased progressively. She had been misdiagnosed with the recrudescence of NHL. The final diagnosis of new-onset SLE was confirmed and a cesarean section was performed at the 34th week of pregnancy. Both the pregnant woman and the newborn were cured with good prognosis. Conclusion: SLE should be considered in a pregnant woman with a medical history of malignancy to rule out other diseases, especially the rheumatic immune diseases.