Lung adenocarcinoma is the most common non-small-cell lung cancer. In this paper, we aim to investigate the expression of chemokine ligand 1 (cx3cl1) and chemokine ligand 28 (CCL28) in spinal metastases of lung adenocarcinoma and their correlation with clinical features and prognosis. We analyzed the clinical data of 40 patients with lung adenocarcinoma and spinal metastases who underwent surgery in our hospital from January 2018 to January 2021 retrospectively. The expression levels of cx3cl1 and CCL28 in bone metastases were detected by immunohistochemistry, and the staining results were sorted and classified. Combined with the follow-up results and clinicopathological data, we statistically analyzed the expression of cx3cl1 and CCL28 in spinal bone metastases and their correlation with prognosis. Among the 40 patients with spinal metastasis of lung adenocarcinoma, 7 cases were strongly positive for cx3cl1, 25 cases were moderately positive, and 8 cases were weakly positive and negative. CCL28 was strongly positive in 9 cases, moderately positive in 26 cases, weakly positive and negative in 5 cases. The expression of cx3cl1 was correlated with ECOG score (P = 0.005) and visceral organ metastasis (P = 0.004), but not with age, sex, and the number of bone metastases (P > 0.05). The expression of CCL28 was correlated with ECOG score (P = 0.022) and visceral organ metastasis (P = 0.003), but not with age, sex, and the number of bone metastases (P > 0.05). The OS of patients with strong cx3cl1 positive was significantly shorter than that of patients with medium positive and weak positive (P < 0.001). The survival time was 10, 7, and 4 months, respectively. The OS of patients with strong positive CCL28 was significantly shorter than that of patients with medium positive and weak positive CCL28 (P = 0.004). The survival time was 12, 8, and 4 months, respectively. Univariate analysis showed that ECOG score (P < 0.001), chemotherapy (P = 0.032), visceral organ metastasis (P = 0.002), cx3cl1 expression (P < 0.001), and CCL28 expression (P = 0.004) were the risk factors of OS. Cox regression analysis showed that the expression of cx3cl1 was an independent risk factor for OS in patients with spinal metastasis of lung adenocarcinoma (P = 0.044). Cx3cl1 and CCL28 were highly/strongly positive in spinal metastases of lung adenocarcinoma. The level of cx3cl1 can be used as an index to judge the clinical prognosis of patients with spinal metastasis of lung adenocarcinoma, which can better reflect the prognosis of patients than CCL28.