Objective To compare the effects of quadratus lumborum block at the lateral supra-arcuate ligament （QLB-LSAL） versus subcostal transversus abdominis plane block （STAPB） on perioperative analgesia and postoperative inflammation in patients undergoing laparoscopic radical resection of colorectal cancer. Methods In this prospective randomized study， we recruited 102 patients undergoing laparoscopic colorectal cancer surgery between October 2022 and October 2024 under general anesthesia and randomly assigned them to two groups： QLB-LSAL （Group Q， n = 51） and STAPB （Group S， n = 51）. Mean arterial pressure （MAP） and heart rate （HR） were recorded before anesthesia induction （T₀）， before surgical incision （T₁）， start of surgery （T₂）， during pneumoperitoneum establishment （T₃）， during peritoneal lavage （T₄）， at the end of surgery （T₅）， and upon leaving the operating room （T₆）. Intraoperative remifentanil consumption， time to first patient-controlled analgesia demand， and frequency of effective compression and rescue analgesia were recorded. Visual Analog Scale （VAS） scores at rest and during coughing were assessed at 24， 48， and 72 hours postoperatively. Interleukin-6 （IL-6） and systemic immune-inflammatory index （SII） at 1 day preoperatively， 1， and 3 days postoperatively were recorded. Postoperative recovery indicators and adverse events were also recorded. Results Group Q demonstrated significantly lower MAP and HR compared with Group S from T₃ to T₆ （P < 0.05）. Group Q had significantly lower intraoperative remifentanil consumption， significantly longer time to first analgesic pump demand， fewer effective pump compression， and lower frequency for rescue analgesia requests （all P < 0.05）. VAS scores at rest and during coughing in Group Q were significantly lower at 24 h and 48 h postoperatively （P < 0.05）. As compared with preoperative levels， both IL-6 and SII increased at 1 and 3 days postoperatively， but magnitude of increase in Group Q was smaller than in Group S （P < 0.05）. In comparison to Group S， Group Q demonstrated significantly earlier ambulation， shorter hospital stay， and fewer adverse events （P < 0.05）. Conclusion QLB-LSAL is superior to STAPB in enhancing perioperative analgesia， attenuating inflammatory response， and accelerating postoperative rehabilitation in patients undergoing laparoscopic colorectal cancer resection.