Objective：To clarify the expression of long non-coding RNA-Human urothelial carcinoma associated 1（LncRNA-UCA），high mobility group box-B1（HMGB1），receptor for advanced glycation end-products（RAGE） and nuclear factor kappa-B（NF-κB） p65 in human non-small cell lung cancer（NSCLC） tissues and normal tissues，and to explore its relationship with the clinical fea－tures and pathological types of NSCLC. Methods：Forty patients with NSCLC admitted to our hospital from May 2018 to August 2018 were enrolled. Cancer tissues and adjacent normal tissues of 40 patients were respectively collected. The expression of HMGB1 and RAGE in cancer tissues and normal tissues 10 patients were detected by immunohistochemistry. The expression of HMGB1，RAGE，NF-κB p65 protein in cancer tissues and normal tissues of 12 patients was detected by Western blot. The mRNA expression of LncRNA-UCA1，HMGB1，RAGE and NF-κB p65 in cancer tissues and normal tissues of 40 patients were determined by quantitative real-time polymerase chain reaction（qRT-PCR）. Results：Immunohistochemistry and Western blot analysis showed that expression of HMGB1（1459.72±366.67） and NF-κB p65（479.52±265.07） in the NSCLC tissues was significantly higher than that in the adjacent normal tissues（847.60±313.66，135.53±109.61）（t=5.470，P=0.000；t=4.063，P=0.002），while expression of RAGE（127.49±43.91） in the NSCLC tissues was significantly lower than that in the adjacent normal tissues（257.61±64.84）（t=-11.461，P=0.000）. The qRT-PCR detection showed that expression of LncRNA-UCA1（4.85±2.31），HMGB1（4.64±2.10） and NF-κB p65（4.22±2.10） in the NSCLC tissues was significantly higher than that in the adjacent normal tissues（1.00±0.00），while expression of RAGE（0.41±0.19） in the NSCLC tissues was significantly lower than that in the adjacent normal tissues（1.00±0.00）（t=-19.754，P=0.000）. The expression of LncRNA-UCA1，HMGB1 and NF-κB p65 in the adenocarcinoma（2.93±1.40，3.06±1.36，2.17±0.87） was higher than that in the squamous cell carcinoma（6.77±2.22，6.16±2.20，5.96±2.90）（t=3.722，P=0.001；t=3.114，P=0.004；t=3.348，P=0.002），in the cancer tissue more than 3 cm（6.70±2.14，6.28±1.80，6.07±2.17） was higher than that in tissues less than 3 cm（3.11±1.40，3.21±1.43，2.28±0.86）（t=-5.367，P=0.000；t=-5.181，P=0.000；t=-5.623，P=0.000），and in cancer tissues with lymph node metastasis（6.38±2.25，6.04±2.25，5.72±2.81） was higher than that in cancer tissues without lymph node metas－tasis（2.70±1.30，3.23±1.38，2.24±0.92）（t=2.377，P=0.023；t=2.404，P=0.021；t=2.410，P=0.021）. The expression of RAGE in adenocarcinoma tissues（0.54±0.18） was lower than that in squamous cell carcinoma tissues（0.28±0.12）（t=-3.049，P=0.004），in tumor tissues more than 3 cm（0.28±0.11） was lower than that in tumor tissues less than 3 cm（0.54±0.18）（t=3.870，P=0.000），and in cancer tissues with lymph node metastasis（0.27±0.11） was lower than that in cancer tissues without lymph node metastasis（0.52±0.18）（t=-2.541，P=0.015）. Pearson correlation analysis showed that in cancer tissues of patients with NSCLC，HMGB1 was positively correlated with expression of LncRNA-UCA1 and NF-κB p65（r=0.754，P=0.000；r=0.704，P=0.000），while RAGE was negatively correlated with expression of HMGB1 and NF-κB p65（r=-0.689，P=0.000；r=0.704，P=0.000）. Conclusion：The high expression of LncRNA-UCA1 is related to the occurrence and development of NSCLC；LncRNA-UCA1 may play a role in influencing HMGB1/RAGE expression and NF-κB pathway.