It is well known that interactions in the tumour microenvironment are very important in the progression of tumours. We investigated the relationship between chemokine ligand type 12 (CXCL12), chemokine receptor type 4 (CXCR4) and survival in advanced colorectal cancers (CRC). Primary tumour samples of stage III-IV CRC patients were investigated for CXCL12 and CXCR4. Chemokine ligand type 12 and CXCR4 expressions were significantly associated with poor prognostic factors (e.g. for CXCL12: lymphatic invasion [p = 0.009], positive surgical margin [p = 0.006], advanced stage [p = 0.028], etc.). Also, these parameters were independent risk factors for low LIR (e.g. for CXCL12: Odds ratio [OR] = 2.27, p = 0.001) and low tumour stroma-ratio (TSR; e.g. for CXCL12: OR = 1.18, p = 0.003). In univariate analysis, 5-year RFS and OS were poor (e.g. for CXCL12: RFS, p < 0.001 and OS, p = 0.001). Multivariate analysis showed that these parameters were independent poor survival parameters for RFS and OS (e.g. for CXCL12: Hazard ratio [HR] = 3.54 [CI: 1.52-4.67], p = 0.001 and HR = 2.74 [1.48-4.71], p = 0.025). We showed that CXCL12 and CXCR4 expressions are poor prognostic factors in lymph node-positive CRC patients and are associated with low TSR and low LIR.