Objective We aimed to detect the expression of cat eye syndrome chromosome region candidate 2 (CECR2) in clear cell renal cell carcinoma (CCRCC), and elucidate the correlation between CECR2 expression and tumor-associated macrophages (TAMs) and its clinicopathological significance. Methods We utilized the TCGA database to analyze the differentially expressed genes (DEGs) in ccRCC, identifying CECR2 as a DEG. Immunohistochemical staining was performed on 112 ccRCC samples and 88 adjacent normal epithelial tissues from the Nanchong Central Hospital to assess CECR2 and TAMs expressions. Statistical methods analyzed the correlation between CECR2, TAMs, and the clinicopathological features of ccRCC. Results Differential analysis based on TCGA database identified that CECR2 was a significantly down-regulated gene. Immunohistochemical staining showed that CECR2 was notably downregulated in ccRCC tissues, with a significantly lower positive rate (11.61%) compared to adjacent normal epithelial tissues (96.69%). Its expression was also significantly associated with WHO/ISUP nuclear grade、T stage, and maximum tumor diameter. Furthermore, the mean infiltration density of M1 macrophages (CD86-positive cells) was significantly lower in ccRCC tissues than in adjacent normal epithelial tissues (4.36/HPF vs 8.99/HPF), whereas M2 macrophages (CD206-positive cells) was significantly higher in ccRCC tissues than in adjacent normal epithelial tissues (16.72/HPF vs4.83/HPF). The infiltration of macrophages in ccRCC was mainly M2 type. Further analysis indicated a significant negative correlation between CECR2 and M2 macrophages (CD206-positive cells) expression, and a significant positive correlation between CECR2 and M1 macrophages (CD86-positive cells) expression in ccRCC tissues. Conclusion CECR2 was significantly down-regulated in ccRCC tissues, and its expression correlated with the distribution of tumor-associated macrophages. CECR2 may influence ccRCC progression by inducing the polarization of M2 macrophages. CECR2 is expected to be a new potential therapeutic target for ccRCC