Objective To evaluate the clinical significance of plasma ionized calcium (ICa) and total calcium (TCa) measurement in diagnosis of tumor-associated hypercalcemia. Methods The heparin lithium anticoagulated plasma were collected and measured with ion selective electrode (ISE) and orthocresolphthalein complexone (OCPC) method for ICa and TCa in 77 patients with malignant tumor (tumor group) and 44 healthy controls (control group). Meanwhile,plasma albumin and pH value were measured to correct TCa (cTCa) and ICa(nICa). The results were analyzed. Results The levels of cTCa,ICa and nICa in tumor group were significantly higher than those in control group(P< 0.01 ) ,but there was no significant difference of TCa between two groups (P > 0.05 ). cTCa > 2.70 mmol/L, nICa > 1.35 mmol/L as the hypercalcemia eritical value, the positive rate of nICa and cTCa were 18.18% (14/77) and 6.49% (5/77)respectively,the difference was significant (P = 0.023). Conclusion Determination of ICa may be more clinical meaningful than TCa for tumor-associated hypercalcemia.