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Objective To explore the relationship between serum miRNA-21 and miR-27b levels and prognosis of patients with renal clear cell carcinoma. Methods A total of 118 patients with renal clear cell carcinoma admitted to the Qinghai University Hospital from February 2019 to April 2021 were selected as the study subjects, and another 118 healthy patients in the same period as the control group. Real time fluorescence quantitative polymerase chain reaction ( PCR) was used to detect the expression of miR-21 and miR-27b in the serum of all subjects. The relative expression levels of serum miR-21 and miR-27b between the patients with renal clear cell carcinoma and healthy control patients were compared. The expression and correlation of serum miR-21 and miR-27b in the patients with renal clear cell carcinoma of different pathological stages and Fuhrman grading were analyzed. The relationship between the expression of serum miR-21 and miR-27b and the survival and prognosis of the patients was explored as well. Results The expression levels of serum miR-21 and miR-27b in the patients with renal clear cell carcinoma were higher than those in the healthy control group (P < 0.05). The serum miR-21 expression level in stage IE patients was higher than in stage I (P < 0.05), while the serum miR-21 expression level in the stage IV patients was higher than that in stages I, II, and IE (P < 0.05). The expression level of miR-27b in the serum of patients gradually increased across the four stages, with a significant difference (P < 0.05). The pathological staging was positively correlated with the expression of miR-21 and miR-27b (P < 0.001). The expression levels of miR-21 and miR-27b in serum of patients gradually increased across grades I, E and IE by Fuhrman grading, with significant difference (P < 0.05). Fuhrman grading was positively correlated with the serum miR-21 and miR-27b expression (P < 0.001). There was a statistically significant difference in the survival curve between the miR-21 high expression group and the low expression group ( P < 0.05 ) . There was a statistically significant difference in the survival curve between the high expression group and the low expression group of miR-27b (P < 0.05). Conclusion The expression levels of serum miR-21 and miR-27b in patients with renal clear cell carcinoma is indicative of the progression and prognosis of the patient's condition. [ABSTRACT FROM AUTHOR]