Objective To observe the occurrence of hypophosphatemia induced by adefovir dipivoxil( ADV) for the treatment of chronic hepatitis B and investigate the association between intact fibroblast growth factor 23( i FGF23) and occurrence of hypophosphatemia,and to find a new way for early discovery and prevention of hypophosphatemic osteomalacia. Methods A total of 1050 patients with chronic hepatitis B and hepatitis B cirrhosis who visited the First Affiliated Hospital of Zhengzhou University from December 2008 to December 2014 were analyzed retrospectively and divided into group A and group B according to different medications. The patients in group A( n = 750) received ADV 10 mg / d and liver protection therapy,and those in group B( n = 300) received entecavir( ETV) 500 mg / d and liver protection therapy,with a median treatment time of 76. 652 ± 5. 053 months. The changes in the levels of serum phosphorus,i FGF23,alkaline phosphatase( ALP),and bone mineral density( BMD) during treatment were collected in the patients in both groups. Chi- square test was applied for comparison of categorical data between the two groups,and Spearman' s rank correlation was applied for correlation analysis. Results In these 1050 patients,47 patients experienced a persistent low level of serum phosphorus,consisting of 46 cases in group A( 4 cases were diagnosed with hypophosphatemic osteomalacia) and 1 case in group B,and group A had a significantly higher incidence of hypophosphatemia than group B( 6. 13% vs 0. 33%; χ2= 16. 859,P < 0. 01). Group A also had significantly higher incidence rates of high i FGF23 and ALP levels and reduced BMD than group B( χ2= 17. 727,10. 823,and 13. 578,respectively,all P < 0. 01). The level of serum phosphorus was negatively correlated with that of i FGF23( r =- 0. 906,P < 0. 01),and was positively correlated with BMD( r = 0. 941,P <0. 01). Conclusion Long- term administration of ADV may cause hypophosphatemia,and high expression of i FGF23 may be related to the occurrence of hypophosphatemia. It is recommended that patients who take ADV for a long time be examined regularly for serum phosphorus,i FGF23,ALP,and BMD.