ABSTRACT Background Long intergenic non-protein coding (lnc) RNA 00305 (LINC00305) is a pro-inflammatory atherosclerosis-associated lncRNA. We hypothesised that LINC00305 expression and its variant rs2850711 (A/T) are implicated in rheumatoid arthritis (RA) and linked with clinical and routine laboratory markers. Methods 100 RA patients and 100 healthy controls were recruited. LINC00305 genotyping and expression were performed using allelic-discrimination PCR and quantitative real-time PCR. LINC00305 diagnostic power was evaluated using area under the receiver operating characteristic curve (AUC). Serum nuclear factor- κB (NF-κB) and matrix metalloproteinase-3 (MMP-3) levels were determined by ELISA, standard laboratory markers by routine methods. Results LINC00305 expression was significantly increased in RA patients and positively correlated with DAS28, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor and anti-cyclic citrullinated peptide antibody. In multivariate analysis, NF-κB, MMP-3 and LINC00305 were significant predictors of RA (P< 0.0001). Individuals carrying AT and TT genotypes of rs2850711 polymorphism had significantly more likely to have RA than AA genotype carriers (P< 0.05). LINC00305 expression, DAS28 score and serum levels of NF-κB and MMP-3 were significantly increased in the patients carrying LINC00305 AT and TT genotypes as compared with AA genotype patients (P< 0.01). Conclusion Increased expression level of LINC00305 and its rs2850711 genetic variant may play a role in the diagnosis and management of RA, and its severity and activity.