To investigate the levels of serum fibroblast growth factor 21 (FGF21) and γ-interferon inducible protein 16 (IFI16) of women with endometriosis (EMT), and to study their diagnostic values for EMT of the women. Methods: 80 women with EMT were selected in study group and 80 healthy women who accepted physical examination were selected in control group from January 2021 to December 2022. The levels of serum FGF21 and IFI16, and the inflammatory factors, such as IL-6, IL-8, and TNF-α, of the women in the two groups were measured by enzyme-linked immunosorbent assay (ELISA). Pearson analysis was used to analyze the correlation between the serum FGF21 and IFI16 levels of the women and their inflammatory factors levels. Multivariate logistic regression was used to analyze the influencing factors of EMT. The values of the serum FGF21 and IFI16 levels for diagnosing EMT was analyzed by the receiver operator characteristic (ROC) curve. Results: The levels of IL-6, IL-8, and TNF-α, and the rates of the dysmenorrhea and abortion of the women in the study group were significantly higher than those of the women in control group. The serum FGF21 level (94.65±13.53 pg/ml) of the women in the study group was significantly lower than that (120.62±16.41 pg/ml) of the women in the control group, the level of IFI16 (16.25±2.73 ng/ml) of the women in the study group was significantly higher than that (12.76±2.19 ng/ml) of the women in the control group. The serum FGF21 level of the women with EMT stage Ⅲ-Ⅳ was significantly lower than that of the women with EMT stage Ⅰ-Ⅱ, and the level of IFI16 of the women with EMT stage Ⅲ-Ⅳ was significantly higher than that of the women with EMT stage Ⅰ-Ⅱ (all P＜0.05). Pearson analysis showed that the serum FGF21 level of the women in the study group were negatively correlated with their IL-6, IL8, and TNF-α levels, while the serum IFI16 level of the women in the study group was positively correlated with their IL-6, IL-8, and TNF-α levels (all P＜0.05). The high FGF21 level of the women was the independent protective factor for their EMT, and the high levels of IFI16, IL-6, IL-8, and TNF-α of the women were the independent risk factors for their EMT (all P＜0.05). The area under the curve (AUC) of the serum FGF21 level and IFI16 level of the women for diagnosing their EMT were 0.875 and 0.838. The AUC of the combined serum FGF21 and IFI16 levels of the women for diagnosing their EMT was 0.932, which was significantly better than that of the serum FGF21 level or the IFI16 level alone (P＜0.05). The specificity and the sensitivity of the combined serum FGF21 and IFI16 levels of the women for diagnosing their EMT were 85.2% and 86.1%. Conclusion: The level of serum FGF21 of the women with EMT is down-regulated and the serum IFI16 level is up-regulated. The combination of the serum FGF21 and IFI16 levels of the women has certain value for diagnosing their EMT.