The prevalence of liver complications is increasing among people living with HIV, and microbial translocation (MT) might play a vital role. We conducted a prospective cohort study to evaluate the association between plasma biomarkers of MT and liver fibrosis (LF) among people living with HIV in southwest China. A total of 665 people living with HIV were enrolled at baseline and had at least one follow-up visit during the 3-year study period. We calculated the Liver Fibrosis Index (FIB-4) to evaluate LF and measured plasma soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP) as surrogate biomarkers for MT. We used ordinal logistic regression to investigate correlates of LF at baseline and used a linear mixed model to examine the association between dynamic changes in MT biomarkers and LF. Of the participants, 61 (9.17%) had advanced LF (FIB-4>3.25), and 193 (29.02%) had moderate LF (1.45 ≤ FIB-4 ≤ 3.25). Patients with advanced LF had higher plasma levels of sCD14 and LBP than those with moderate or no LF, both at baseline and at follow-up. The following factors were significantly associated with advanced LF: the highest quartile of LBP (adjusted odds ratio [aOR]=1.69; 95% confidence interval [CI] 1.02~2.81), current intravenous drug use (aOR=1.82; 95% CI 1.06~3.12), baseline CD4 <200 cells/μl (aOR=3.25; 95% CI 2.13~4.95), hepatitis C virus coinfection (aOR=2.52; 95% CI 1.41~4.51) and age >50years (aOR=32.66; 95% CI 15.89~66.36). LF progression (increasing FIB-4) was significantly associated with increasing sCD14level (β=1.11; 95% CI 0.97~1.26; p<0.001) with covariate adjustment. The significant relationship between MT and LF may reveal pathogenic mechanisms and potential intervention targets of liver complications among people living with HIV in China.