Objective To explore the pathological mechanism of high mobility group protein B1 (HMGB1) expression in early spontaneous abortion induced by inflammatory factors, and to provide clinical reference. Methods 40 cases of early spontaneous abortion admitted to Zhuhai Center For Maternal and Child Health Care from August 2021 to December 2022 were selected as the study group, and 40 cases of surgical termination of pregnancy were selected as the control group for retrospective analysis. The placental tissues of the two groups were collected, and the expressions of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) and HMGB1 in the placental tissues of the two groups were compared, and the correlation between TNF-α, IL-1, IL-6 and HMGB1 expression was analyzed. Results The levels of TNF-α, IL-1, IL-6 and HMGB1 in placental tissues of the study group were higher than those in the control group (P<0.05). The levels of TNF-α, IL-1 and IL-6 in human villus tissue blocks in the study group were higher than those in the control group (P<0.05). The average number of blood vessel formation per cm2 in human villus tissue blocks in the study group was higher than that in the control group (P<0.05). Correlation analysis showed a positive correlation of TNF- α, IL-1 and IL-6 levels with HMGB1 expression (P<0.05). Conclusion The expression levels of inflammatory factors and HMGB1 in early spontaneous abortion are higher, and are positively correlated with the expression of HMGB1 , which is an important pathological basis of early spontaneous abortion.