Objective To detect the genetic mutations of solid tumors with a 50-gene hotspot mutational panel,and to interrogate the genetic mutation profiling of solid tumors. Methods A total of 367 various types of solid tumor samples were collected,and the genetic mutation with a 50-gene hotspot mutational panel based on BES 4000 platform was determined. Results Among the 367 solid tumor samples,64.03% samples had at least one gene mutation. Different genetic mutations in 28 genes were determined,and the most frequency mutated genes were EGFR(32.15%),TP53(15.53%),K-ras(8.17%),c-kit(5.72%),APC(3.00%),PTEN(3.00%),B-raf(2.72%),ERBB2(2.72%) and PIK3CA(2.72%). In non-small cell lung cancer(NSCLC),the most frequency mutated gene was EGFR(40.10%),and EGFR mutation just harbored in NSCLC patients. TP53 mutation was found at NSCLC,colorectal cancer,gastric cancer and ovarian cancer patients,and the mutation frequencies were 13.61%,34.38%,33.30% and 50.00%,respectively. K-ras(42.86%) was the most frequency mutated gene in colorectal cancer patients,and that in gastrointestinal stromal tumor was c-kit(53.13%). Among 235 gene mutation samples,28.97%(68/235) had at least 2-gene comutation,and TP53 comutation rate was the highest as 16.60%(39/325). There was no correlation between whether harbored gene mutation and sex,age. The mutation rate of TP53 in ≥58-year-old patients was higher than that <58-year-old patients(P<0.001). In NSCLC,females(P<0.01) and patients with adenocarcinoma(P<0.001) were prone to carry EGFR mutation,and <58-year-old patients were prone to carry ERBB2 mutation. Conclusions Different genetic mutation profiling is determined in solid tumors,TP53 mutation is found in various types of solid tumors and is correlated with patients' age. Target-based next generation sequencing can identify the genetic mutation profiling in solid tumors and provide a reference for clinical treatment.