Objective: To study the effect of hydromorphone applied in the gynecological laparoscopic operation and analyze its effect on the hemodynamics and inflammatory cytokines. Methods: A total of 170 patients who were underwent selective gynecological laparoscopic operation under general anesthesia were included in the study and randomized into the observation group (n=85) and the control group (n=85). On the basis of routine anesthesia, the patients in the observation group were given hydromorphone, while the patients in the control group were given fentanyl. The hemodynamic changes in different timing points in the two groups were observed and compared. The levels of serum inflammatory cytokines and stress reaction indicators in the two groups were detected and compared. Results: HR, SBP, and MAP at T2 in the observation group were significantly reduced when compared with at T1, those at T3 were recovered to levels at T1. HR, SBP, and MAP at T2 and T3 in the control group were significantly reduced, and those were significantly lower than those in the observation group. IL-6, IL-10, and TNF-α levels 24 h after anesthesia in the two groups were significantly elevated when compared with before anesthesia. IL-10 level in the observation group was significantly higher than that in the control group, while IL-6 and TNF-α were significantly lower than those in the control group. CRP, FC, A, and NE levels 24 h after anesthesia in the two groups were significantly reduced, and those in the observation group were significantly lower than those in the control group. Conclusions: Hydromorphone applied in the gynecological laparoscopic operation will not produce great effect on the hemodynamics, with small stress reaction and mild inflammatory reaction; therefore, it is more beneficial for the postoperative recovery.