To study the effect of multimodal preemptive analgesia on the levels of inflammatory factors, pain mediators, and stress hormone, and immune function of patients with abdominal hysterectomy. Methods: 110 patients who underwent abdominal hysterectomy were selected and divided into control group and observation group (55 cases in each group) according to different analgesic methods from January 2015 to December 2018. The patients in the control group were given postoperative analgesia, while the patients in the observation group were given multimodal preemptive analgesia. The visual analogue scale (VAS) score, the levels of serum inflammatory factors, such as TNF-α, IL-6 and IL-10, the levels of serum pain mediators, such as substance P (SP), prostaglandin E2 (PGE2), β-endorphin (β-EP), the levels of serum stress hormone, such as adrenaline (NE), angiotensin II (Ang II), cortisol (Cor), and the levels of immune function index, such as IgG, IgM and IgA of the patients at 6h, 12h, 24h and 48h after operation were compared between the two groups. Results: At 6h, 12h, 24h and 48h after operation, the VAS score, and the levels of TNF-α, IL-6, IL-10, SP and PGE2 of the patients in the observation group were significant lower than those of the patients in the control group, but the levels of β-EP, IgG, IgM and IgA of the patients in the observation group were significant higher (P＜0.05). At 48h after operation, the levels of TNF-α, IL-6, IL-10, SP and PGE2 of the patients in the observation group were significant lower than those in the control group, but the levels ofβ-EP, IgG, IgM and IgA of the patients in the observation group were significant higher (P＜0.05), while there was no significant difference in VAS score of the patients between the two groups (P＞0.05). Conclusion: Multimodal preemptive analgesia can inhibit the secretion of inflammatory factors of patients with abdominal hysterectomy and reduce their inflammatory response effectively. The pain symptom of patients is relieved by reducing the secretion of pain mediators, and the stress response of patients is decreased by inhibiting the secretion of stress hormones. The immune function of patients has also been improved.