Appropriate cycle number of perioperative chemotherapy for patients with locoregionally advanced rectal cancer (LARC) remains unknown. This study aimed to evaluate how cycle number of perioperative chemotherapy influenced the prognosis of LARC patients. In this study, a total of 388 consecutive patients were enrolled and retrospectively reviewed if they were diagnosed with untreated stage cII-III LARC and treated with neoadjuvant chemoradiotherapy plus radical surgery followed by adjuvant chemotherapy or not. After grouping by the postoperative pathologic stage (yp0-I vs. ypII-III), propensity score matching was performed in each group to balance baseline characteristics between the patients treated with chemotherapy cycle ≤ 7 and those treated with chemotherapy cycle ≥ 8. The chemotherapy cycle was analyzed for its association with the survivals of the matched patients in the 2 groups, respectively. And the incidence of treatment-related complications was also compared. Through analysis, chemotherapy cycle ≥ 8 appeared to predict better overall, disease-free and distant-metastasis-free survivals in the whole cohort of matched patients ( values were 0.003, 0.002 and 0.004, respectively) and the ypII-III group ( values were 0.006, 0.005 and 0.014, respectively). But in the yp0-I group, chemotherapy of 8 cycles or more brought no improvement of survivals but only more acute toxicities (83.5% vs. 57.0%, < 0.001). Chemotherapy cycle ≥ 8 was proven associated with improved prognosis of LARC patients, especially those with ypII-III disease. But prolonged chemotherapy should be performed with caution in patients with yp0-I stage.