To study the effect of ultrasonic-guided serratus plane block combined with pectoral nerve block Ⅰ on postoperative analgesia after radical mastectomy. A total of 30 patients, all female, aged [ ()] 53 (43, 62) years old, who underwent radical mastectomy in Beijing Tongren Hospital from May to August 2021 were selected. The patients were divided into two groups (=15 in each group) using a random number table: general anesthesia alone+patient controlled intravenous analgesia (PCIA) group (control group) and serratus plane block combined with pectoral nerve block Ⅰ before general anesthesia+PCIA group (combined group). Numerical rating scale (NRS) at rest in both groups were detected in the post anesthesia care unit (PACU) and 4, 8, 12, 24, 36 and 48 h after operation. The time of first pain, the time of first pressing of the automatic analgesic device after the operation, the dosage of remifentanil during operation, cumulative dosages of sufentanil at 24 h and 48 h postoperatively, and the incidence of adverse effects were all recorded. The NRS scores in combined group in the PACU and 4, 8, 12 and 24 h after surgery were (2.1±1.7), (1.7±1.5), (1.5±1.4), (1.5±1.3) and (1.7±1.3), respectively, while the NRS scores in control group at each time points were (4.5±2.0), (3.2±1.4), (2.7±0.9), (2.8±0.9) and (2.4±0.8), respectively, and the NRS scores in combined group were significantly lower than those in control group (all <0.05). The NRS scores in combined group at 36 and 48 h after surgery were (1.8±1.6) and (1.6±1.2), while the NRS scores in control group were (2.2±0.9) and (2.1±0.8), and the differences between the two groups were not statistically significant (both >0.05). The time of first pain and the time of the first pressing of the automatic analgesic device in combined group were (573±174) min and (962±313) min, which were significantly longer than those of control group [(13±6) min and (135±41) min] (both <0.05). The dosage of remifentanil during operation and cumulative dosage of sufentanil at 24 h postoperatively in combined group were (410±129) μg and (14±4) μg, which were lower than those in control group [(580±225) μg and (21±11) μg] (both <0.05). Cumulative dosage of sufentanil at 48 h postoperatively in combined group was (29±11) μg, while in control group was (36±14) μg, and the difference between the two groups was not statistically significant (=0.131). The incidence of postoperative dizziness in combined group was 6.7% (1/15), which was lower than that of control group [40.0% (6/15)] (=0.031). The incidence of nausea and pruritus was 6.7% (1/15) and 0 in combined group, while 20.0% (3/15) and 6.7% (1/15) in control group, with no statistical significance (both >0.05). Serratus plane block combined with pectoral nerve block Ⅰ can effectively relieve postoperative pain, decrease the need for opioids, and reduce the incidence of adverse effects.