Objective To understand the prognosis of patients with bone metastases from first-treatment non-small cell lung cancer （NSCLC） of different pathological types after different first-line treatment regimens， in order to provide clinical prediction of disease progression， guidance of treatment， and improvement of prognosis. Methods 403 NSCLC patients with bone metastases who received primary treatment with bone metastases from Chaohu Hospital of Anhui Medical University from 1 January 2019 to 31 December 2023 were selected for univariate analysis using survival analysis （Log-rank test） and multifactorial analysis with Cox regression， and it was found that histopathological subtyping was an independent factor affecting the prognosis of patients （P = 0.001， HR = 1.952）， after which the effect of this factor on prognosis was removed， and the total number of patients was divided into two groups according to histopathological classification： adenocarcinoma group （316） and squamous carcinoma group （87）， and then multifactorial analysis was performed again using Cox regression model to analyse the factors affecting survival prognosis. Results In this data analysis， patients with the pathological type of squamous carcinoma had a median overall survival （mOS） of 15 months （95% CI： 12.85 ~ 17.15） and a median progression-free survival （mPFS） of 9 months （95% CI： 7.34 ~ 10.67）， whereas patients in the adenocarcinoma group had a mOS of 25 months （95% CI： 23.26 ~ 26.74） and mPFS was 16 months （95% CI：14.43 ~ 17.57）， a statistically significant difference. The OS of the overall group was affected by multiple factors， including Eastern Cooperative Oncology Group （ECOG） score status （1/> 1） at the time of initial diagnosis， bone metastases to Trunk + limb bones + cranium， number of bone metastases ≥ 4， mutation of ALK target genes， and the use of chemotherapy+targeted therapy as the first line of treatment. therapy； similarly， PFS was also affected by the above factors. In addition， in the adenocarcinoma and squamous carcinoma models based on histopathological classification， chemotherapy + targeted therapy and chemotherapy + immunotherapy were found to be the protective factors for the two groups， and ALK target gene mutation was only a protective factor for the adenocarcinoma group. Conclusion This study further confirmed the prognostic factors influencing the prognosis of patients with bone metastases from primary NSCLC， which provides an important reference for clinical treatment.