Abstract: [Objective] To search the method of determining the anatomic reduction of the first metatarsal cuneiform joint during open reduction and internal fixation (ORIF) of Lisfranc injury. [Methods] A retrospective study was conducted on 74 patients who received ORIF for closed Lisfranc fracture and dislocation in our hospital from January 2011 to December 2019. Of them, 35 patients in the earlier stage had a single criterion (SC) used in ORIF, which was anatomic restoration of the dorsal and medial cortices alignment, while 39 patients in the later stage had combined criteria (CC) used, in which hallux tibial sesamoid position on the anteroposterior fluoroscopy was added based on abovesaid standard to avoid the rotation of the first metatarsal. The perioperative, follow-up and imaging data of the two groups were compared. [Results] All patients in both groups had operation performed successfully without serious complications. There were no significant differences in operation time, total incision length, intraoperative blood loss, intraoperative fluoroscopy times, walking time, incision healing and hospital stay between the two groups (P>0.05). The end point of postoperative follow-up was of 10~14 months postoperatively, before removal of internal fixation. The CC group regained full weight-bearing activity significantly earlier than the SC group [(61.6±9.0) days vs (69.2±7.2) days, P<0.001]. At the last follow-up, the rest VAS score and walking VAS score significantly decreased (P<0.05), while the AOFAS middle foot score was significantly increased in both groups (P<0.05). At the last follow-up, the CC group proved significantly superior to the SC group in terms of VAS score [(1.4±1.0) vs (2.7±1.5), P<0.001] and AOFAS score [(98.2±3.9) vs (95.5±6.0), P=0.025]. As for imaging, the step-off sign (SOS), C1-M2 space, M1-M2 space, C1-C2 space, Meary Tomeno angle and Hardy-Clapham sesamoid scale in both groups significantly reduced at the last follow-up compared with those preoperatively (P<0.05). At the last follow-up, the CC group got significantly less Hardy-Clapham sesamoid scale than the SC group [(2.6±0.5) vs (4.7±0.9), P<0.001]. [Conclusion] Anatomical reduction is the key to Lisfranc surgical treatment. The alignment of dorsal and medial cortices of the first metatarsal cuneiform joint, combined with the position of the hallux tibial sesamoid, can ensure the sagittal, coronal and rotational anatomical reduction of the first metatarsal cuneiform joint.