This retrospective study evaluated the safety and efficacy of SURGICEL® Powder–Absorbable Hemostatic Powder (SP) made from oxidized regenerated cellulose (ORC) in total knee arthroplasty (TKA). Ninety-one patients who underwent TKA at Peking University Third Hospital between January 2024 and July 2024 were retrospectively analyzed. Hemostatic effectiveness was evaluated by comparing perioperative blood loss, hemoglobin (Hb) levels, hematocrit (HCT), and transfusion rates. Clinical safety was assessed by comparing complication rates, operation time, visual analog scale (VAS) scores, and postoperative fever. Finally, 85 patients were included: 43 in the SP group (using SP) and 42 in the control group (not using SP). There were no significant differences in age, sex, height, weight, preoperative HCT, or Hb levels. The volume of perioperative blood loss within 3 days in the SP group was reduced by approximately 154 ml compared with that in the control group. The Hb and HCT levels in the SP group were higher on the first, second, and third days after surgery, and there were significant differences between the two groups in terms of repeated measurements of HCT and Hb levels within 3 days postoperatively. There were no statistically significant differences in the operation time, postoperative VAS scores, complications, transfusion rates, or postoperative fever. In conclusion, this study confirmed that SP can significantly reduce perioperative blood loss in TKA without negatively affecting clinical outcomes.