CYTL1 is a novel cytokine that was first identified in CD34(+) hematopoietic cells. We previously prepared recombinant CYTL1 and verified that it chemoattracted human monocytes via the CCR2/ERK pathway. It has been reported that CYTL1 plays contradictory roles in neuroblastoma and lung cancer. We found that the expression level of CYTL1 was notably decreased and it was hypermethylated in various tumors, including breast and lung cancer, by bioinformatics analyses. After validating the expression of CYTL1 in lung cancer, we identified that CYTL1 exerted no obvious effect on tumor cell proliferation but inhibited their migration and invasion, and these effects were accompanied by decreasing STAT3 phosphorylation, using recombinant CYTL1 and CYTL1-overexpressing tumor cell lines. Furthermore, we constructed experimental and spontaneous metastasis models of breast cancer in BALB/c mice and found that CYTL1 significantly inhibited tumor metastasis in vivo. In summary, CYTL1 is a cytokine with tumor-suppressing characteristics that inhibits tumor metastasis and STAT3 phosphorylation in multiple types of tumors.