Background and Purpose: Recently, intensive care unit acquired weakness (ICUAW) has become a hotspot issue in the patients with critical illness. The symptoms of ICUAW, including sensory impairment and muscle atrophy, may lead to poor quality of life even though the patients discharged from the ICU for a long time. Therefore, early evaluation is necessary to keep critically ill patients away from ICUAW. Medical Research Council (MRC) scale is the most common approach for diagnosis clinically. Regarding the interrater variation of MRC, handgrip strength (HGS) has been thought to be a simple and accurate alternative. However, HGS does not belong to antigravity or respiratory muscles which are the first to be affected by immobilization. It is still unknown whether HGS can represent the general muscle condition in the ICU or not. The aim of this study was to investigate the association between handgrip strength and muscle thickness of quadriceps and diaphragm in ICU patients. Methods: This was a prospective and observational study. Patients in the surgery intensive care unit of Taoyuan General Hospital were recruited and evaluated in 48 hours from ICU admission. The frequency of the evaluation was one time a day until the patients discharged from the ICU. The outcome measures included HGS assessed by electronic hand dynamometer and muscle thickness of diaphragm and quadriceps detected by ultrasound. The diaphragm thickness data were measured at the end of expiration and inspiration. Spearman's correlation tests were conducted to investigate the association between HGS and muscle thickness every single day. A significance level of p was < 0.05. Results: A total of 389 patients (mean age 62.6 ± 17.4; 33% female) were recruited in the study. HGS had fair correlation (r = 0.372-0.581) with muscle thickness of rectus femoris and vastus intermedius in the first week. HGS significantly correlated (r = 0.493-0.678) with diaphragm thickness in the second week. However, the sample sizes after 10th day were small (n < 20). Conclusion: Hand dynamometer is a feasible tool to estimate the antigravity muscle thickness of the ICU patients who stay less than 1 week. For the patients with a long ICU stay, handgrip strength may be a parameter to assess diaphragm conditions and assist clinicians to make the decision about ventilator weaning. Clinical Relevance: According to the results of our study, HGS correlated with the different muscles in the different timings of the ICU stay. The study finding could provide an evident base for clinical practice.