Two male patients (patient 1,54 years old;patient 2,63 years old) were treated with apatinib mesylate tablets (apatinib) for adenocarcinoma of cardia and gastric fundus and left lung cancer,respectively.Patient 1 developed erythema and swelling on the extremities,perianal,and perigenital on day 22 after taking apatinib (850 mg/d).Apatinib-induced hand-foot skin reaction (HFSR) was considered.Then apatinib was discontinued,oral vitamin B6 and topical external vitamin E cream were given.After withdrawal of apatinib,his skin symptoms alleviated,and apatinib (750 mg/d) was re-given on day 7 after withdrawal.On day 57 after the resumption of apatinib,the patient's skin symptoms worsened and the medication was discontinued again.Afterwards,apatinib was given and then discontinued for 2 times (first 500 mg/d and then 250 mg/d).Because the symptoms aggravated after medication and alleviated after discontinuation,apatinib treatment was terminated finally.Patient 2 developed skin erythema,swelling,and pain on the palms and soles on day 35 after apatinib treatment at a dose of 500 mg/d.On day 85,he developed skin desquamation and circular keratosis of hands and feet,scattered erythema with desquamation in axilla,perianal region and groin,and increased pain in the skin lesions.Apatinib-induced HFSR was diagnosed.Apatinib was discontinued and symptomatic treatments were given.On day 17 of drug withdrawal,his skin symptoms improved and apatinib (500 mg/d) was given again.About 2 weeks later,the patient's skin symptoms aggravated again,and the drug was discontinued.