Objective To investigate the expressions and clinical significances of chemokine receptor 4 (CXCR4) and chemokine ligand 12 (CXCL12) in hypopharyngeal squamous cell carcinoma (HSCC).Methods A total of 90 patients with HSCC admitted from January 2017 to November 2022 were selected as the study objects, and their HSCC tissues and adjacent tissues were used as the experimental materials. The expressions of CXCR4 and CXCL12 in HSCC tissues and adjacent tissues were detected by immunohistochemical staining. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect CXCR4 mRNA and CXCL12 mRNA levels in HSCC tissues and adjacent tissues. The clinicopathological characteristics of HSCC patients were collected and recorded, and the relationships between the expression levels of CXCR4 and CXCL12 and the clinicopathological characteristics of patients were analyzed. Pearson analysis was applied to analyze the correlation between CXCR4 and CXCL12 levels.Results The expression rate of CXCR4 in HSCC tissues was 60.00%, which was significantly higher than that in adjacent tissues (17.78%) (P＜0.05). The expression rate of CXCL12 in HSCC tissues was 57.78%, which was obviously higher than that in adjacent tissues (24.44%) (P＜0.05). The expression levels of CXCR4 and CXCL12 in HSCC tissues were correlated with lymph node metastasis, TNM stage and differentiation (P＜0.05). Compared with the adjacent tissues, the levels of CXCR4 and CXCL12 in HSCC tissues were significantly increased (P＜0.05). Pearson analysis showed that CXCR4 level was positively correlated with CXCL12 level in HSCC patients (r=0.538, P＜0.05).Conclusion CXCR4 and CXCL12 are highly expressed in HSCC tissues, which are related to lymph node metastasis, differentiation degree and TNM stage of HSCC.