Objective To investigate the clinical distribution, drug resistance and clonal transmission of Haemophilus influenzae (H. influenzae) isolated from children with pneumonia in Haikou City, and provide a theoretical basis for the prevention and treatment of H. influenzae pneumonia in children. Methods Clinical data of 5 342 hospitalized children with pneumonia in Haikou Hospital of the Maternal and Child Health in 2021 were collected. Positive rate of H. influenzae from children's respiratory tract specimens was calculated, and drug resistance and homology of multilocus sequence typing (MLST) of strains were analyzed. Results 352 H. influenzae strains were isolated from 5 342 children with pneumonia, with an isolation rate of 6.59%. Isolation rates of H. influenzae of male and female children were 7.10% and 5.82% respectively; isolation rates of H. influenzae of children at the age of < 30 days, 30 days-, 2 years-, 4 years-, and ≥ 6 years were 0.30%, 8.45%, 11.62%, 12.88% and 2.56% respectively, with a statistically significant difference among all age groups(P < 0.05). Isolation rates in spring, summer, autumn, and winter were 14.04%, 4.48%, 4.62%, and 4.40% respectively, seasonal difference was statistically significant (P < 0.001). Positive rate of H. influenzae β-lactamase was 42.60% (141/331). Resistance rates of H. influenzae to compound sulfamethoxazole, ampicillin, and cefuroxime were 76.43%, 69.19%, and 51.36% respectively, to azithromycin, amoxicillin/clavulanic acid, ceftazidime, and ceftriaxone were all < 30%, to meropenem and levofloxacin were < 1%. 51 H. influenzae strains were divided into 15 ST types by MLST sequencing, including 11 strains (21.57%) of ST107, which mainly distributed among children aged 4 months-1 year (9 strains) and 3 years (2 strains). Conclusion H. influenzae isolated from children with pneumonia in Haikou City is genetically diverse and transmitted through community cloning. Most children with pneumonia were aged 2-3 years old. Spring is the peak season of high infection incidence. ST107 is dominant in spring. Empiric treatment with compound sulfamethoxazole, ampicillin and cefuroxime should be cautious. Resistance to amoxicillin/clavulanic acid and resistance of β-lactamase negative strains to ampicillin increased, which should be paid attention in clinic.