Objective To investigate the correlation between the ratio of lesion volume to uterine volume （T/U）， the expression levels of Ki-67 and p16 proteins in lesion tissue， and the recurrence risk of endometrial cancer. Methods A total of 150 patients diagnosed with endometrial carcinoma through pathological examination at Qiandongnan Prefecture People's Hospital were enrolled for follow-up observation. Among them， 28 patients experienced recurrence after a 2-year follow-up period， while 122 patients remained recurrence-free. The expression differences of Ki-67 protein and p16 protein in T/U and lesion tissues during surgery were compared between the two groups. Furthermore， these indexes were analyzed based on different pathological features， and the variation in relapse-free survival time was assessed among patients with distinct T/U status as well as Ki-67 and p16 protein expressions. Results The T/U value and the positive expression rate of Ki-67 protein were significantly higher in the relapsed group compared to the non-relapsed group， while the positive expression rate of p16 protein was significantly lower in the relapsed group （P < 0.05）. Additionally， patients with T/U ≥ 0.18 had a significantly higher proportion of stage Ⅲ patients and patients with low histological differentiation compared to those with T/U < 0.18 （P < 0.05）. Furthermore， patients with positive expression of Ki-67 protein exhibited a significantly higher proportion of stage Ⅲ patients， patients with low histological differentiation， and lymph node metastasis compared to those with negative expression of Ki-67 protein （P < 0.05）. The proportion of stage Ⅲ patients exhibiting positive p16 protein expression， low histological differentiation， and lymph node metastasis was significantly lower compared to those with negative p16 protein expression （P < 0.05）. Patients with endometrial cancer having a T/U ≥ 0.18 experienced shorter recurrence-free survival time 2 years post-surgery in comparison to patients with T/U < 0.18 （χ² = 6.962， P = 0.008）. Patients displaying positive Ki-67 expression had a shorter recurrence-free survival time 2 years after surgery than those with negative Ki-67 expression （χ² = 4.815， P = 0.028）. The recurrence-free survival time 2 years after surgery for patients expressing p16 protein positively was longer than that for patients expressing it negatively （χ² = 4.279， P = 0.039）. The presence of FIGO stage Ⅲ， lymph node metastasis， depth of myographic invasion ≥1/2， T/U value ≥ 0.18， and positive expression of Ki-67 protein were identified as significant risk factors for postoperative recurrence in endometrial cancer （P < 0.05）. Conversely， the positive expression of p16 protein was found to be a protective factor against recurrence in endometrial carcinoma following surgery （P < 0.05）. Conclusion The expression of T/U， Ki-67 protein， and p16 protein in endometrial cancer patients is associated with tumor progression and may augment the risk of postoperative recurrence.