Scrub typhus is an acute zoonotic infectious disease caused by Orientia tsutsugamushi. The clinical manifestations of the disease are fever, rash, lymph node enlargement, the presence of specific eschar and ulcer at the bitten site are the most important basis for diagnosis of the disease, patients without eschar and ulcer are often difficult to be identified. This article reports a 54 year old male patient with fever, lymph node enlargement and multiple organ damage as the main clinical manifestations, whose diagnosis was difficult due to the absence of cha-racteristic scabs and poor curative effect of empirical use of antimicrobial agents. The pathogen was clearly identified as Orientia tsutsugamushi after metagenomic next-generation sequencing (mNGS). After treated with levofloxacin and azithromycin, patient's symptoms improved quickly, finally recovered and discharged from hospital. mNGS has been proved more sensitive than traditional culture methods, and superior to traditional clinical methods in early diagnosis of tsutsugamushi disease, especially for patients without typical eschar.