Objective To investigate the effects of different administration routes of tranexamic acid on perioperative blood loss, and hemoglobin (Hb) and hematocrit (HCT) levels in elderly patients with femoral intertrochanteric fracture treated undergoing closed reduction and proximal femoral nail anti-rotation (PFNA) internal fixation. Methods A total of 122 elderly patients with femoral intertrochanteric fracture admitted to Chaohu Hospital of Auhui Medical University from June 2020 to May 2022 were selected, all patients were treated with closed reduction and PFNA internal fixation, according to the random number table method, patients were divided into the control group (33 cases, didn’t applied tranexamic acid), the intraoperative local administration group (32 cases, locally applied tranexamic acid during operation), the preoperative intravenous administration group (26 cases, injected intravenously tranexamic acid 30 min before the operation), and the combined administration group (31 cases, locally applied during operation combined with preoperative intravenous administration of tranexamic acid). The dominant blood loss, total blood loss, recessive blood loss, operation time, and the levels of Hb and HCT before and 1, 3, 5 d after operation were compared among the 4 groups. Results Compared with the control group, the dominant blood loss, total blood loss and recessive blood loss significantly reduced in the intraoperative local administration group, preoperative intravenous administration group and combined administration group, and the above indexes in the combined administration group were significantly lower than those in the preoperative intravenous administration group and the intraoperative local administration group; compared with before operation, the levels of Hb and HCT of patients in the 4 groups decreased significantly from 1 to 5 days after operation, compared with the control group, the levels of Hb and HCT of patients in the intraoperative local administration group, the preoperative intravenous administration group and the combined administration group increased significantly at each time point after operation, but the combined administration group was significantly higher than the intraoperative local administration group and the preoperative intravenous administration group (all P<0.05). There was no statistically significant difference in the dominant blood loss, total blood loss and recessive blood loss of patients, the level of Hb and HCT from 1 to 5 days after operation of patients between the local administration group and the intravenous administration group, and the operation time, the incidence of thrombus 1 month after operation of patients among the 4 groups (all P>0.05). Conclusion Tranexamic acid applied in the operation of elderly patients with femoral intertrochanteric fracture by the combination of intraoperative local administration and preoperative intravenous, which can play a good hemostatic effect, and has little influence on the blood system, so as to prevent the occurrence of thrombosis and anemia.