Background: Colorectal cancer (CRC) ranks as the third most prevalent malignancy globally and represents a leading cause of cancer-related mortality worldwide. CXCL12, an essential chemokine, has been demonstrated to be critically involved in cancer metastasis. Aldolase A (ALDOA) is a crucial glycolytic enzyme that contributes to cellular energy production and has been implicated in tumor metabolism and tumor progression. Objective: This study aimed to identify of CXCL12 and ALDOA immunohistochemical expression in CRC cases and correlation of their expression with clinicopathological data and patient's survival of the studied cases to detect their potential prognostic role. Material and methods: This retrospective study included 40 cases CRC immunohistochemically stained with CXCL12 & ALDOA and the results to be correlated with different clinicopathological variables and patient's survival. Results: High CXCL12 expression was positively associated with positive lympho-vascular invasion (P=0.001), tumor budding (P=0.027), deeper tumor invasion (P=0.016), positive lymph node metastasis (P=0.000), presence of distant metastasis (P=0.036) and greater tumor stage (P=0.001). High ALDOA expression was positively associated with high tumor grade (P=0.030), positive lympho-vascular invasion (P=0.005), positive perineural invasion (P= 0.020), high tumor budding (P=0.030), higher tumor stage (P=0.002) and positive lymph node metastasis (P=0.001). Elevated CXCL12 and ALDOA expression levels were indicative of poor five-year overall survival (P=0.017 and 0.044 respectively) as well as poorer disease-free survival (P=0.016 and 0.002 respectively). Conclusion: CXCL12 and ALDOA overexpression was correlated with poor prognosis and poor patient's survival in CRC. Therefore, their expression could predict prognosis and survival of the patient, and blocking their pathways may provide new promising treatment strategies in CRC.