Objective To investigate the expression levels and clinical significance of serum long non-coding RNA (LncRNA) X inactive specific transcript (LncRNA XIST) and microRNA-141-3p (miR-141-3p) in patients with kidney stones.Methods A total of 100 patients with kidney stones admitted to Kailuan General Hospital Linxi Hospital from April 2018 to December 2022 taken as the kidney stones group, and 100 healthy subjects were included as the control group. The levels of serum LncRNA XIST, miR-141-3p, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and osteopontin(OPN) in the kidney stones group and the control group were compared. The correlation of serum LncRNA XIST and miR-141-3p expression levels with IL-1β, TNF-α and OPN in patients with kidney stones, and the correlation between serum LncRNA XIST expression levels and miR-141-3p were analyzed. The adverse prognosis of patients with kidney stones within 21 days after retrograde intrarenal surgery was recorded, and the patients were divided into a poor prognosis group (24 cases) and a good prognosis group (76 cases) according to the prognosis, the general data and serum levels of LncRNA XIST, miR-141-3p, IL-1β, TNF-α and OPN in patients with kidney stones with different prognosis were compared. The influencing factors of the prognosis of patients with kidney stones were analyzed. Results Compared with the control group, the serum levels of LncRNA XIST, IL-1β, TNF-α and OPN were increased in the kidney stone group, while the expression level of miR-141-3p was decreased (all P<0.05). The results of Pearson analysis showed that the expression level of serum LncRNA XIST in patients with kidney stones was positively correlated with IL-1β, TNF-α and OPN (r=0.507, 0.396, 0.472, all P<0.05). The expression level of miR-141-3p was negatively correlated with IL-1β, TNF-α and OPN (r=-0.483, -0.414, -0.458, all P<0.05). The expression level of serum LncRNA XIST in patients with kidney stones was negatively correlated with miR-141-3p (r=-0.463, P<0.05). Compared with the good prognosis group, the levels of serum LncRNA XIST, IL-1β, TNF-α and OPN in the poor prognosis group were increased, while the expression level of miR-141-3p was decreased (all P<0.05). LncRNA XIST, IL-1β, TNF-α and OPN were risk factors affecting the prognosis of patients with kidney stones (all P<0.05), and miR-141-3p was a protective factor affecting the prognosis of patients with kidney stones (P<0.05).Conclusions The expression of serum LncRNA XIST is up-regulated and the expression of miR-141-3p is downregulated in patients with kidney stones. LncRNA XIST and miR-141-3p may be auxiliary indicators for early diagnosis of kidney stones and evaluation of prognosis of patients.