〔Abstract〕 Objective To investigate the changes and clinical significance of hemoglobin (HB) and serum ferritin (SF) in pregnant women with thalassemia. Methods 60 pregnant women with thalassemia treated in Guangdong Maternal and Child Health Hospital from March 2019 to October 2020 were selected as the observation group, and 60 healthy pregnant women who underwent physical examination in our hospital in the same period were selected as the control group. The changes and decreasing ranges of Hb and SF levels in different pregnancy periods of the two groups were measured and compared, and the pregnancy outcomes of the two groups were compared. Results The level of Hb in the observation group was lower than that in the control group at different pregnancy stages, and the decrease range of Hb was higher than that in the control group with statistical significance (P < 0.05). There was no significant difference in SF level between the observation group and the control group in the early stage (P > 0.05); The levels of SF in the observation group were lower than those in the control group in the middle and late stages, and the decline range of SF was higher than that in the control group (P < 0.05). The amount of postpartum hemorrhage in the observation group was significantly higher than that in the control group (P < 0.05); The weight of newborns in the observation group was significantly lower than that in the control group (P < 0.05); The proportion of abnormal amniotic fluid volume in the observation group was 20.00%, which was higher than 8.33% in the control group (P < 0.05); The proportion of premature infants in the observation group was 15.00%, which was higher than 5.00% in the control group, the difference was statistically significant (P < 0.05); The proportion of cesarean section in the observation group was 48.33%, which was higher than 30.00% in the control group, the difference was statistically significant (P < 0.05). Conclusion The levels of Hb and SF in pregnant women with thalassemia during pregnancy are low, which has a serious adverse impact on the outcome of mothers and infants. Clinically, we should always observe the changes of Hb and SF levels, find abnormalities in time and give treatment.