Objective To explore the role of extracellular secretory protein sulfatase-1 (SULF1) in colon cancer prognosis and immune cell infiltration. Methods SULF1 gene expression level in tumor and normal tissues was identified via Oncomine database and Tumor Immune Estimation Resource (Timer) site. The correlation between SULF1 gene expression level and colon cancer prognosis was obtained by Prognoscan database and Gene Expression Profiling Interactive Analysis (GEPIA). The relationship for SULF1 geneexpression level in colon cancer immune cell infiltration and tumor-associated macrophage surface markers was retrieved by Timer database gene module and gene correlation module. The results were further verified by GEPIA database. Results The results of Timer and Oncomine database analysis indicated that SULF1 was highly expressed in colon cancer. The results of Prognoscan chip GSE17536 and GEPIA database showed that the high expression of SULF1 was positively correlated with the poor prognosis of colon cancer. SULF1 was positively correlated with the infiltration of colon cancer immune cells CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells, and not associated with B cells. SULF1 had the strongest positive correlation with macrophages (r=0.628), and the correlation with M2-type macrophages was significantly higher than that with M1-type macrophages. Conclusion SULF1 is highly expressed and positively correlated with poor prognosis in colon cancer. The tumor-associated macrophage infiltration may be one of involved mechanisms.